Ipilimumab Monotherapy for Melanoma: A Nursing Toolkit ...themelanomanurse.org/wp-content/uploads/2019/05/MNI-toolkit-IPI-… · melanoma and as an adjuvant treatment of resected

Ipilimumab (Yervoy®) is a monoclonal antibody directed against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), one of the checkpoints that regulates the immune system. CTLA-4 is a negative regulator of T-cell activation and proliferation, which means that it turns the immune response “off.” Ipilimumab binds to CTLA-4, essentially cutting the brake, thereby enabling the immune system to remain “on” and better attack developing cancers.

Ipilimumab is indicated as a monotherapy for unresectable or metastatic (advanced) melanoma and as an adjuvant treatment of resected stage 3 melanoma. Ipilimumab is also indicated in combination with nivolumab (Opdivo®) for the treatment of unresectable or metastatic melanoma (discussed in a separate nursing tool).

This document is part of an overall nursing toolkit intended to assist nurses in optimizing management of melanoma patients receiving newer anti-melanoma therapies.

Ipilimumab Monotherapy for Melanoma: A Nursing Toolkit From the Melanoma

Nursing Initiative (MNI)

© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org

© 2017 The M

elanoma N

ursing Initiative. All rights reserved

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Inspired By Patients . Empow

ered By Knowledge . Im

pacting Melanom

a

• A higher ipilimum

ab dose and longer treatment duration is em

ployed when ipilim

umab is used as an adjuvant therapy than as a m

onotherapy foradvanced m

elanoma. The regim

ens are indicated below:

DRUG-DOSING/ADMINISTRATION

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Inspired By Patients . Empow

ered By Knowledge . Im

pacting Melanom

a

• Obtain pretreatm

ent laboratory tests (eg, adrenal function [ACTH

], clinical chemistries, liver function tests, and thyroid function tests) prior to

initiation of therapy and before each cycle

• Ipilimum

ab is a clear to opalescent, colorless to pale-yellow solution. D

iscard the vial if solution is cloudy, discolored, or contains extraneousparticulate m

atter (other than a few translucent-to-w

hite, proteinaceous particles)

• Do not shake the vial and do not coadm

inister ipilimum

ab with other drugs through the sam

e intravenous line. It is important to assure IV access

before administration. Adm

inister ipilimum

ab through an intravenous line containing a sterile, non-pyrogenic, low-protein-binding in-line filter (w

erecom

mend a pore size of 0.2–4 m

icrometers)

DRUG-DOSING/ADMINISTRATION

Note: A recent phase 3 study report from

ASCO

2017 indicated an adjuvant ipilimum

ab dose of 10 m

g/kg was associated w

ith higher rates of treatment-related adverse events than a low

er 3 mg/kg

dose in patients with resected high-risk m

elanoma, w

ithout improving recurrence-free survival.

(CONTINUED)

• Key to toxicity management:» Proactive assessment for early signs/symptoms of toxicity» Prompt intervention» irAEs are typically managed with selective use of steroids» In rare instances, toxicity may be steroid refractory, and additional immunosuppressive agents

may be necessary (mycophenolate mofetil, cyclophosphamide, etc)» Ipilimumab will likely be held or discontinued depending on severity and/or persistence» Referral to organ specialist should be considered

• irAEs associated with ipilimumab treatment can be categorized into those that are most common, lesscommon but serious, and others that are easily overlooked

• Table 1 lists these irAEs and the corresponding Care Step Pathways in Appendix 1. Other adverseevents associated with ipilimumab are shown in Appendix 2


Because ipilimumab is an immunotherapy that works by enhancing the patient’s immune system, most adverse reactions associated with ipilimumab are related to overactivity of the patient’s immune system (ie, immune-related adverse events [irAEs]). Various organ systems (often more than one) or tissues may be affected.

Inspired By Patients . Empowered By Knowledge . Impacting Melanoma

SIDE EFFECTS AND THEIR MANAGEMENT

irAE category Examples Location

Most common

Skin toxicities (pruritis, rash)Gastrointestinal toxicities

- Mild diarrhea/colitis - Mucositis/xerostomia

Hepatic toxicities - Elevated transaminases

Appendix 1

Less common but serious

Endocrinopathies - Hypophysitis (pituitary) - Thyroiditis - Diabetes

Pneumonitis

Appendix 1

Easily overlookedArthralgia/arthritis NeuropathyNephritis

Appendix 1

Table 1. Care Step Pathways for the Management of Immune-Related AEs Associated With Ipilimumab Monotherapy

• Ipilimumab-related irAEs may occur at any time, including after treatment completion ordiscontinuation. Continuing to monitor patients is critical

• Patients sometimes experience signs/symptoms that they think are due to “flu” or a cold, but thatactually represent an irAE or an infusion reaction

• Endocrinopathies often present with vague symptoms (fatigue, headache, and/or depression) thatcan easily be overlooked or initially misdiagnosed. Hypervigilance and follow-up is important on the part of both nurses and patients

• IrAEs may become apparent upon tapering of corticosteroids, since they can be suppressed ormasked by immunosuppressive therapy. Patients should be advised to be on the lookout for early signs of irAEs during the tapering period

• Unlike other irAEs, endocrinopathies usually do not resolve and may require lifelong hormonereplacement therapy

• Nurses should encourage patients to carry information about their ipilimumab regimen with themat all times. This might be the ipilimumab-specific wallet card, or at least emergency phone numbers and the side effects associated with the regimen. You may suggest that they paperclip the wallet and insurance cards together so information about their regimen will be shared whenever they show their insurance card

• Advise patients to take pictures of any skin lesions for documentation


CLINICAL PEARLS


Q. Is ipilimumab monotherapy still being used in the advanced melanoma setting?

A. Yes. While PD1 inhibitors and the combination of ipilimumab and nivolumab are more typicallyused, there are some patients who still receive ipilimumab monotherapy for unresectable ormetastatic melanoma. In fact, the ipilimumab label was recently expanded to include use inpediatric patients age 12 and older with advanced melanoma.

Q. How do I counsel my patients about immunizations?

A. That’s a logical question, given that the checkpoint inhibitors alter the immune response.Advise your patients not to receive live vaccines (eg, measles, mumps, and rubella and the varicella vaccine [Zostavax®]) because they have not been evaluated in this setting. The use of attenuated vaccines has been and continues to be evaluated. Counsel patients to discuss all immunizations with the oncology team prior to administration so the benefits and risks can be weighed on an individual basis. For example, Shingrix®, approved in 2017, is an attenuated (non-live) varicella vaccine, which can be discussed with the oncology team if a recommendation is being made for the patient to receive the injection series.


QUESTIONS & ANSWERS


Financial AssistanceBMS Access Support 1 (800) 861-0048 http://www.bmsaccesssupport.bmscustomerconnect.com/patient

Additional Information ResourcesAIM at Melanoma Foundation (Nurse on Call, patient symposia, drug resources, etc) http://www.AIMatMelanoma.org

American Cancer Society Resource Section https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html

PATIENT RESOURCES

http://www.bmsaccesssupport.bmscustomerconnect.com/patient

http://www.AIMatMelanoma.org

http://www.AIMatMelanoma.org

https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html

https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html

https://www.cancer.org/cancer/melanoma-skin-cancer/treating/immunotherapy.htm


• Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13:473-486.

• Food and Drug Administration & Bristol-Myers Squibb. Risk Evaluation andMitigation Strategy (REMS) for ipilimumab (Yervoy); February 2012. Includes wallet card etc. Available at: https://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM249435.pdf

• Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-relatedadverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016;2:1346-1353.

• Madden KM, Hoffner B. (2017). Ipilimumab-based therapy: consensus statement fromthe faculty of the Melanoma Nursing Initiative on managing adverse events with ipilimumab monotherapy and combination therapy with nivolumab. Clin J Oncol Nurs. 2017;21(suppl):30-41.

• Rubin KM. Managing immune-related adverse events to ipilimumab: a nurse’s guide.Clin J Oncol Nurs. 2012;16:E69-E75.

• Villadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update onmanagement of immune-related toxicities. Transl Lung Cancer Res. 2015;4:560-577.

• Yervoy® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2017.Available at: http://packageinserts.bms.com/pi/pi_yervoy.pdf

ADDITIONAL RESOURCES

Click here for downloadable action plans to customize for your patients

https://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM249435.pdf

https://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM249435.pdf

http://packageinserts.bms.com/pi/pi_yervoy.pdf

http://themelanomanurse.org/yervoy-ipilimumab-action-plan/

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APPENDIX 1

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Care Step Pathw

ay-Skin Toxicities

Nursing Assessm

ent

Look:-

Does the patient appear uncom

fortable?-

Does the patient appear unw

ell?-

Is there an obvious rash?-

Is the patient scratching during the visit?-

Is skin integrity intact?-

Are there skin changes?o

Xerosiso

Changes in skin pigm

ent or color-

Is there oralinvolvement of the rash?

Grading Toxicity

MAC

ULO

PAPU

LAR

RA

SH (aka m

orbilliformrash)

Definition: A

disorder characterized by the presence of macules (flat) and papules (elevated); frequently affecting the upper trunk, spreading centripetally

and associated w

ith pruritus

PRU

RITU

SD

efinition: A disorder characterized by an intense itching sensation

Listen:-

Does the patient have pruritus

with or w

ithout rash?Is there a rash w

ith or without pruritus ?

-A

re symptom

s interfering with A

DLs?

-W

ith sleep?-

Have sym

ptoms w

orsened?

Recognize:

-Is there a history of derm

atitis, pre-existing skinissues (psoriasis, w

ounds, etc.)?-

Laboratory abnormalities consistent w

ith otheretiologies (e.g., eosinophils on com

plete bloodcount, liver function abnorm

alities)

Managem

ent

Overall Strategy

-Assess for other etiology of rash: ask patient about new

medications,herbals, supplem

ents, alternative/complem

entarytherapies, lotions, etc.

Grade 1 (M

ild)-

Imm

unotherapyto continue

-O

ral antihistamines w

ill be used in som

e patients-

Topicalcorticosteroids will be used in

some patients (0.5 m

g/kg)-

Advise vigilant skin care o

Increase to twice daily

applications of non-steroidalm

oisturizersor em

ollientsapplied to m

oist skino

Moisturizers w

ith ceramides and

lipids are advised;however, if

cost is an issue, petroleumjelly

is also effectiveo

Soothing m

ethods

Cool cloth applications

Topicals w

ith cooling agentssuch as m

enthol orcamphor

R

efrigerating products priorto application

oA

void hot water;bathe orshow

erw

ith tepid water

oK

eep fingernails shorto

Cool tem

peraturefor sleep

-A

dvise strict sun protection -

Monitor vigilantly. Instruct patient &

family to call clinic w

ith any sign ofw

orsening rash/symptom

s. Anticipate

office visit for evaluation-

Assess patient&

family

understanding of skin care recom

mendations and rationale

oIdentify barriers to adherence

Grade 2 (M

oderate)-

Ipilimum

ab will be w

ithheld forany Grade

2 event-

Oral corticosteroids (0.5

mg/kg–1.0m

g/kg)and oralantihistam

ines/oral anti-pruriticsto be used

-C

onsider dermatology consult

-P

atient education:o

Proper adm

inistration of oralcorticosteroids

Take with food

Take early in day

C

oncomitant m

edications may

be prescribed

H2 blocker

A

ntibiotic prophylaxis-

Advise vigilant skin careo

Gentle skin care

oTepid baths;oatm

eal baths-

Advise strict sun protection

-A

ssesspatient &

family understanding of

toxicity and rationale for treatmenthold


Grades 3-4 (Severe or Life-Threatening)

-N

ivolumab

to be withheld forG

rade 3 rash orconfirm

edS

JN or TE

N-

Ipilimum

ab to be discontinued for any Grade

3/4 event, and nivolumab forG


ed SJS

or TEN

-P

embrolizum

ab or nivolumab to be

discontinued for any Grade 3/4 event that

recurs, persists≥12 w

eeks, orfor inability to reduce steroid dose to ≤10 m

g prednisone orequivalent w

ithin 12 weeks

-A

nticipate hospitalization and initiation of IVcorticosteroids (1.5–2.0

mg/kg)

-A

nticipate dermatology consult +/-biopsy

-P

rovide anticipatory guidance: o

Rationale for hospitalization and

treatment discontinuation

oR

ationale for prolonged steroid tapero

Side

effects ofhigh-dose steroidso

Risk

of opportunistic infectionand

need for antibiotic prophylaxis

oE

ffectson

blood sugars, muscle

atrophy, etc.-

Assess

patient &fam

ily understanding oftoxicity and rationale for treatm

entdiscontinuation o

Identify barriers to adherence,specifically com

pliance with steroids

when transitioned to oral corticosteroids

Grade 1 (M

ild)M

acules/papules covering <10%

BS

Aw

ith or without sym

ptoms

(e.g., pruritus, burning, tightness)

Grade 2 (M

oderate)M

acules/papules covering 10-30%B

SA

with or w

ithout symptom

s (e.g.,pruritus, burning, tightness); lim

iting instrum

ental AD

Ls

Grade 3 (Severe)

Macules/papules covering >30%

B

SA

with or w

ithout associated sym

ptoms; lim

iting self-care ADLs;

skin sloughing covering <10%

BS

A

Grade 4 (Potentially Life-Threatening)

Papules/pustules covering any %

BS

A w

ith or w

ithout symptom

s and associated with

superinfection requiring IV antibiotics; skin

sloughing covering 10-30% BS

A

Grade 5 (D

eath)

Grade 1 (M

ild)M

ild or localized; topical intervention indicated

Grade 2 (M

oderate)Intense or w

idespread; interm

ittent; skin changes from

scratching (e.g., edema,

papulation, excoriations, lichenification, oozing/crusts); lim

iting instrumental A

DLs

Grade 3 (Severe)

Intense or widespread; constant;

limiting self-care A

DL or sleep


Grade 5 (D

eath)

Intervention in at-risk patients-

Advise gentle skin care:o

Avoid soap. Instead,use non-soap

cleansersthat are fragrance-and

dye-free (use mild soap on the

axillae, genitalia, and feet)o

Daily applications

of non-steroidalm

oisturizersor em

ollientscontaining hum

ectants (urea,glycerin)

oA

pplym

oisturizers and emollients

in the direction of hair growth to

minim

ize development of folliculitis

-A

dvise sun-protective measures

-A

ssess patient& fam

ilyunderstanding

ofprevention strategies and rationaleo

Identify barriers to adherence

RED FLAGS:

-Extensive

rash (>50% BSA), or rapidly progressive

-O

ral involvement

-Concern for suprainfection

AD

Ls = activities ofdaily living;BS

A=

bodysurface area;S

JN=

Stevens-Johnson syndrom

e; TEN

=toxic

epidermal necrolysis

Copyright ©

2017 Melanom

a Nursing Initiative.

Skin Toxicities Page 1 of 2

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elanoma N


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elanomanurse.org

Care Step Pathw

ay-Skin Toxicities

Nursing Assessm

ent

Look:-


fortable?-


ell?-

Is there an obvious rash?-

Is the patient scratching during the visit?-

Is skin integrity intact?-

Are there skin changes?o

Xerosiso

Changes in skin pigm

ent orcolor-

Is there oralinvolvement of the rash?

Grading Toxicity

MAC

ULO

PAPU

LAR

RA

SH (aka

morbilliform

rash)D

efinition: Adisorder characterized by

the presence ofmacules (flat) and papules (elevated); frequently

affecting the upper trunk, spreading centripetallyand associated

with pruritus

PRU

RITU

SD

efinition: Adisorder characterized by an intense itching sensation

Listen:-

Does the patient have pruritus

with or w

ithout rash? Is there a rash w

ith or withoutpruritus?

-A

re symptom

s interfering with A

DLs?

-W

ith sleep? -

Have sym

ptoms w

orsened?

Recognize:

-Is there a history ofderm

atitis, pre-existing skin issues (psoriasis, w

ounds, etc.)?-

Laboratory abnormalities consistent w

ith otheretiologies (e.g.,eosinophils

on complete blood

count, liver function abnormalities)

Managem

ent

Overall Strategy

-Assess for other etiology of rash: ask patient about new

medications, herbals, supplem

ents, alternative/complem

entary therapies, lotions, etc.

Grade 1 (M

ild)-

Imm

unotherapy to continue-

Oral antihistam

ines will be used in

some patients

-Topical corticosteroids w

ill be used in som

e patients -


Increase to twice daily

applications of non-steroidal m

oisturizers or emollients

applied to moist skin

oM

oisturizers with ceram

ides and lipids are advised; how

ever, if cost is an issue, petroleum

jelly is also effective

oS

oothing methods

C

ool cloth applications

Topicals with cooling agents

such as menthol or cam

phor

Refrigerating products prior

to applicationo

Avoid hot w

ater; bathe or shower

with tepid w

atero

Keep fingernails short

oC

ool temperature for sleep

-A

dvise strict sun protection-

Monitor vigilantly. Instruct patient &

family to call clinic w

ith any sign of w

orsening rash/symptom

s. Anticipate

office visit for evaluation-

Assess patient &

family

understanding of skin care recom



Grade 2 (M

oderate)-

Ipilimum

ab will be w

ithheld for any Grade 2

event-

Oral corticosteroids (0.5 m

g/kg–1.0 mg/kg)

and oral antihistamines/oral anti-pruritics to

be used-

Consider derm

atology consult-

Patient education:o

Proper adm

inistration of oral corticosteroids

Take with food

Take early in day

C

oncomitant m

edications may be

prescribed

H2 blocker

A

ntibiotic prophylaxis-


Gentle skin care

oTepid baths; oatm

eal baths-

Advise strict sun protection

-A

ssess patient & fam

ily understanding of toxicity and rationale for treatm

ent holdo



-N

ivolumab

to be withheld for G


edS

JN or TE

N-

Ipilimum

ab to be discontinued for any Grade

3/4 event, and nivolumab for G


ed SJS

or TEN

-P

embrolizum

ab or nivolumab t o be

di scontinued for any Grade 3/4 event that

recurs, persists ≥12 weeks, orfor inability to

r educe steroid dose to ≤10 mg prednisone or

equivalent within 12 w

eeks-

Anticipate hospitalization and initiation of IV

corticosteroids (1.5–2.0m

g/kg)-

Anticipate derm

atology consult +/-biopsy-

Provide anticipatory guidance:o

Rationale for hospitalization and


oR

ationale for prolonged steroid tapero

Side

effects of high-dose steroidso

Risk of opportunistic infection and

needf or antibiotic prophylaxis

oE

ffects on blood sugars, muscle

at rophy, etc.-

Assess patient &


toxicity and rationale for treatment

discontinuationo

Identify barriers to adherence,specifically com

pliance with steroids

when transitioned to oral corticosteroids

Grade 1 (M

ild)M

acules/papules covering <10%

BS

Aw

ith or without sym

ptoms

(e.g., pruritus, burning,tightness)

Grade 2 (M

oderate)M

acules/papules covering 10-30%B

SA

with or w

ithout symptom

s (e.g.,pruritus, burning,tightness); lim

iting instrum

entalAD

Ls

Grade 3 (Severe)

Macules/papules covering >30%

B

SA

with or w

ithout associated sym

ptoms;lim

iting self-care ADLs;

skin sloughing covering <10%

BS

A


Papules/pustules covering any %

BS

A w

ith or w

ithout symptom

sand associated w

ith superinfection requiring IV

antibiotics; skin sloughing covering 10-30%

BSA

Grade 5 (D

eath)

Grade 1 (M

ild)M

ild or localized; topicalintervention indicated

Grade 2 (M

oderate)Intense or w

idespread;interm

ittent; skin changesfrom

scratching (e.g., edema,

papulation, excoriations,lichenification, oozing/crusts);lim

iting instrumental A

DLs

Grade 3 (Severe)

Intense or widespread;constant;

limiting self-care A

DL orsleep


Grade 5 (D

eath)

Intervention in at-risk patients-

Advise gentle skin care:o

Avoid soap. Instead, use non-soap

cleansers that are fragrance-anddye-free (use m

ild soap on theaxillae, genitalia, and feet)

oD

aily applications of non-steroidalm

oisturizers or emollients

containing humectants (urea,

glycerin)o

Apply m

oisturizers and emollients

in the direction of hair growth to

minim

ize development of folliculitis

-A

dvise sun-protective measures

-A

ssess patient & fam

ily understandingof prevention strategies and rationaleo


RED FLAGS:

-Extensive rash (>50%

BSA), or rapidly progressive-

Oral involvem

ent-

Concern for suprainfection

AD

Ls = activities of daily living; BS

A=

body surface area;SJN

=S

tevens-Johnson syndrome; TE

N = toxic epiderm

al necrolysis

Copyright ©

2017 Melanom


Skin Toxicities Page 2 of 2

Care Step Pathw

ay -Gastrointestinal Toxicity: D

iarrhea and Colitis

Nursing Assessm

entLook:-

Does the patient appear w

eak?-

Has the patient lost w

eight?-

Does the patient appear dehydrated?

-D

oes the patient appear in distress?

Grading Toxicity

Diarrhea (increased frequency, loose, large volum

e, or liquidy stools)

Colitis (inflam

mation of the intestinal lining)

Listen:-

Quantity &

quality of bowel m

ovements (e.g., change in/

increased frequency over baseline): solid, soft, or liquiddiarrhea; dark or bloody stools; or stools that float

-Fever

-A

bdominal pain or cram

ping-

Increased fatigue-

Upset stom

ach, nausea, or vomiting

-B

loating/increased gas-

Decreased appetite or food aversions

Recognize:

-S

erum chem

istry/hematology abnorm

alities-

Infectious vs imm

une-related adverse eventcausation

-P

eritoneal signs of bowel perforation (i.e.,

pain, tenderness, bloating)

Managem

ent(including Anticipatory G

uidance)

Overall Strategy:

-R

ule out infectious, non-infectious, disease-related etiologies

Grade 1 (M

ild)-

May continue im

munotherapy

Diet m

odifications (very important):

-Institute bland diet;decrease fiber, uncooked fruits/vegetables, red m

eats, fats, dairy, oil, caffeine,alcohol, sugar

Grade 2 (M

oderate)-

Send stool sam

ple forC difficile

testing, culture, andova and

parasite -

Imm

unotherapyto be w

ithhelduntil G

rade ≤1 orpatient’sbaseline (ipilim

umab, pem

brolizumab, nivolum

ab)-

Provide anti-diarrheals: Im

odium®

(loperamide)orLom

otil ®

(diphenoxylate/atropine)-

Ifupper orlower G

Isymptom

spersist >5–7 days

oO

ral steroids* to be started (prednisone 0.5m

g–1m

g/kg/day or equivalent)o

After control of sym

ptoms, a ≥4-w

eek steroid* taper will

be initiated-

Imm

unotherapyto

be discontinued ifGrade 2

symptom

spersist≥6 w

eeks (ipilimum

ab)or≥12 w

eeks (pembrolizum

ab,nivolum

ab),or for inability to reduce steroid dose to ≤7.5 mg

(ipilimum

ab) or≤10 m

g prednisone or equivalent(pem

brolizumab, nivolum

ab) within 12 w

eeks

Diet m

odification:-

Institute bland dietlow in fiber, residue,and fat (B

RA

T[B

ananas, Rice, A

pplesauce,Toast] diet)-

Decrease fiber, uncooked fruitand vegetables, red m

eats,fats,dairy, oil,caffeine, alcohol, sugar

-A

void laxativesor stool softeners

-A

dvance diet slowly

assteroids

are tapered,* reduced to lowdoses

and assessfor loose or liquid stoolfor severaldays or

longer-

Steroids* to be tapered slow

ly over at least 4 weeks

(Moderate) persistent orrelapsed

symptom

s with steroid*

taper-

Consider gastroenterology consultfor possible intervention

(flex sig/colonoscopy/endoscopy)-

IV steroids*

to be started at1m

g/kg/day-

Imm

unotherapyto

be helduntil≤G

rade 1-

Controlsym

ptoms, then ≥4-w

eeksteroid* taper

-R

ecurrent diarrhea is more likely w

hen treatmentis

restarted

Grades 3-4

(Severe or Life-Threatening)-

Onset: o

Continued dietm

odification, anti-diarrheals,and steroidtitration

-Im

munotherapy:

oG

rade 3: Pembrolizum

abor nivolum

abto be w

ithheld w

hen used as singleagent;ipilim

umab

to be discontinued

as single agent andnivolum

ab when given

with ipilim

umab

oG

rade 4: Ipilimum

ab and/or PD-1 inhibitorto be

discontinued-

Does

of steroids*to

be increased:o

Steroids* 1-2 m

g/kg/day prednisone orequivalent:m

ethylprednisolone (Solu-M

edrol ®)1 g IV(daily

divided)doses

-H

ospitalization-

GI consultation

-A

ssess forperitoneal signs, perforation (NP

O &

abdominalx-

ray, surgical consultprn)-

Use caution w

ith analgesics (opioids) and anti-diarrhealm

edications

Steroid* refractory:(if not responsive w

ithin 72 hours to high-dose IV

steroid* infusion)-

Infliximab

(Rem

icade®)5

mg/kg infusion

may

be considered-

May

require ≥1 infusion to manage sym

ptoms

(may

re-adm

inister at week 2 &

week

6)-

Avoid w

ith bowelperforation or sepsis

-P

PD

(tuberculin)testing not required in this setting -

Infliximab infusion delay m

ay have life-threatening consequences

Diet m

odification:-

Very strict w

ith acute symptom

s:clear liquids;verybland, low

fiberand low residue (B

RA

T diet)-

Advance dietslow

ly as steroids* reduced to low doses

-S

teroids*to be tapered slow


-Supportive

medications

for symptom

atic managem

ent:o

Loperamide:2

capsulesatthe onset &

1 with each

diarrhea stoolthereafter, with a m

aximum

of 6 perdayo

Diphenoxylate/atropine 1-4

tabletsper day

oS

imethicone

when necessary

Grade 1 (M

ild)A

symptom

atic; clinical or diagnosticobservation only; intervention not indicated

Grade 2 (M

oderate)A

bdominal pain;blood or m

ucus in stoolG

rade 3 (Severe)Severe abdom

inal pain; change in bow

el habits; medical intervention

indicated; peritonealsigns


Life-threatening(e.g., hem

odynamic

collapse); urgent intervention indicated

Grade 5 (D

eath)

Nursing Im

plementation:

-C

ompare baseline assessm

ent:grade & docum

ent bowel frequency

-E

arly identification and evaluation of patient symptom

s-

Grade sym

ptom &

determine level ofcare and interventions required

-E

arly intervention with lab w

ork and office visit ifcolitissym

ptoms are

suspected

*Steroid

taperinstructions/calendarasa

guidebutnotan

absolute-

Tapershouldconsiderpatient’s

currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas

gastriculcerprevention

while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges

(anger,reactive,hyperaware,euphoric,m

ania),increasedappetite,interrupted

sleep,oralthrush,fluidretention

-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-termhigh-dose

steroids:-

Considerantim

icrobialprophylaxis(sulfam

ethoxazole/trimethoprim

double dose M/W

/F; single dose ifuseddaily) or alternative ifsulfa-allergic (e.g.,atovaquone [M

epron®]1500 m

g podaily)

-C

onsideradditionalantiviraland antifungalcoverage-

Avoid

alcohol/acetaminophen

orotherhepatoxins

Grade 1 (M

ild)-

Increase of <4 stools/day overbaseline

-M

ild increase in ostomy output

compared w

ithbaseline

Grade 2 (M

oderate)-

Increase of 4–6 stools/day overbaseline

-M

oderate increase of output inostom

y compared w

ithbaseline

Grade 3 (Severe)

-Increase of ≥7 stools/day

overbaseline; incontinence

-H

ospitalization indicated-

Severe increase in ostom

y outputcom

pared with

baseline-

Limiting self-care A

DLs


-Life-threatening

(e.g., perforation, bleeding,ischem

ic necrosis, toxic megacolon)

-U

rgent intervention required

Grade 5 (D

eath)

RED FLAGS:

-Change

in gastrointestinalfunction, decreased appetite-

Bloating, nausea-

More frequent stools, consistency

change fromloose to liquid

-Abdom

inal pain-

Fever

AD

Ls = activities ofdaily living;PD

-1=

programm

ed cell death protein 1

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Gastrointestinal Toxicity Page 1 of 3

Care Step Pathw

ay-G

astrointestinal Toxicity:Diarrhea

and Colitis

Nursing Assessm

entLook:-


eak?-


eight?-


-D


Grading Toxicity


e, or liquidystools)

Colitis (inflam

mation of the intestinallining)

Listen:-

Quantity &

quality of bowelm

ovements

(e.g., change in/increased frequency over baseline): solid, soft,or liquid diarrhea;dark orbloody stools;or stools that float

-Fever

-A


ping-

Increased fatigue-

Upset stom

ach,nausea,or vomiting

-A


ping-

Bloating/increased gas

-D

ecreased appetite orfood aversions

Recognize:

-S

erum chem


alities-

Infectious vsim

mune-related adverse event

causation-

Peritonealsigns

of bowel perforation (i.e.,


Managem


uidance)

Overall Strategy:

-R


Grade 1 (M

ild)-

May continue im

munotherapy

Diet m


-Institute bland diet;decrease fiber, uncookedfruits/vegetables, red m

eats, fats, dairy, oil,caffeine, alcohol, sugar

Grade 2 (M

oderate)-

Send stool sam

ple for C difficile


parasite-

Imm

unotherapy to be withheld until G

rade ≤1 or patient’sbaseline (ipilim

umab, pem

brolizumab, nivolum

ab)-


odium®

(loperamide) orLom

otil ®


Ifupper or lower G

I symptom

s persist >5–7 dayso

Oral steroids* to be started (prednisone 0.5

mg–1

mg/kg/day or equivalent)

oA

fter control of symptom

s, a ≥4-week steroid* taper w

illbe initiated

-Im

munotherapy to be discontinued ifG

rade 2sym

ptoms

persist≥6 weeks (ipilim

umab) or ≥12 w

eeks (pembrolizum

ab,nivolum

ab), or for inability to reduce steroid dose to ≤7.5 mg

(ipilimum

ab) or ≤10 mg prednisone or equivalent

(pembrolizum

ab, nivolumab) w

ithin 12 weeks

Diet m

odification:-

Institute bland diet low in fiber, residue, and fat (B

RA

T[B

ananas, Rice, A

pplesauce, Toast] diet)-


eats,fats, dairy, oil, caffeine, alcohol, sugar

-A

void laxatives or stool softeners-

Advance diet slow

ly as steroidsare tapered,* reduced to low

dosesand assess for loose or liquid stool for several days or

longer-



(Moderate) persistent or relapsed sym

ptoms w

ith steroid* taper-

Consider gastroenterology consult for possible intervention


IV steroids*

to be started at1m

g/kg/day-

Imm

unotherapyto be held

until ≤Grade 1

-C

ontrol symptom

s, then ≥4-week

steroid* taper-

Recurrent diarrhea is m

ore likely when treatm

ent isrestarted

Grades 3-4


Onset:o

Continued diet m

odification, anti-diarrheals, and steroid titration

-Im

munotherapy:

oG

rade 3: Pem

brolizumab or nivolum

ab to be withheld

when used as single agent; ipilim

umab to be

discontinued as single agent and nivolumab w

hen given w

ith ipilimum

abo

Grade 4: Ipilim

umab and/or P

D-1 inhibitor to be

discontinued-

Dosage of steroids* to be increased:o

Steroids* 1-2 m

g/kg/day prednisone or equivalent: m


edrol ®)1 g IV (daily divided)

doses-

Hospitalization

-G

I consultation-

Assess for peritoneal signs, perforation (N

PO

& abdom

inal x- ray, surgical consult prn)

-U

se caution with analgesics (opioids) and anti-diarrheal

medications



steroid* infusion)-

Infliximab

(Rem

icade®)5

mg/kg infusion

may be considered

-M

ay require ≥1 infusion to manage sym

ptoms (m

ay re-adm

inister at week 2 &

week 6)

-A

void with bow

el perforation or sepsis-

PP

D(tuberculin) testing not required in this setting

-Inflixim

ab infusion delay may have life-threatening

consequences

Diet m

odification:-

Very strict w

ith acute symptom

s:clear liquids;very bland, lowfiber and low

residue (BR

AT diet)

-A

dvance diet slowly as steroids* reduced to low

doses-



-Supportive m

edicationsfor sym

ptomatic m

anagement:

oLoperam

ide:2capsules

at the onset & 1 w

ith eachdiarrhea stool thereafter, w

ith a maxim

um of 6 per day

oD

iphenoxylate/atropine 1-4tablets

per dayo

Sim

ethiconew

hen necessary

Grade 1 (M

ild)A

symptom

atic; clinical ordiagnosticobservation only;intervention notindicated

Grade 2 (M

oderate)A

bdominal pain;blood orm

ucus in stoolG


inal pain; change inbow





odynamic


Grade 5 (D

eath)

Nursing Im

plementation:

-C


ent:grade & docum

ent bowel frequency

-E


s-

Grade sym

ptom &

determine level ofcare and interventions required

-E


ork and office visit ifcolitissym

ptoms are

suspected

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-termhigh-dose

steroids:-

Considerantim



double dose M/W

/F; single dose ifuseddaily) or alternative ifsulfa-allergic (e.g.,atovaquone [M

epron®]1500 m

g podaily)

-C


Avoid


orotherhepatoxins

Grade 1 (M

ild)-


-M


compared

with

baseline

Grade 2 (M

oderate)-

Increase of4–6 stools/day overbaseline

-M

oderate increase of outputinostom

y compared w

ithbaseline

Grade 3 (Severe)

-Increase of≥7 stools/day


-H



youtput

compared

with

baseline-


DLs


-Life-threatening


icnecrosis, toxic

megacolon)

-U


Grade 5 (D

eath)

RED FLAGS:

-Change

in gastrointestinalfunction, decreased appetite-

Bloating, nausea-

More frequent stools, consistency

change fromloose to liquid

-Abdom

inal pain-

Fever

AD

Ls = activities ofdaily living;PD

-1=

programm


Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org


Care Step Pathw

ay-G

astrointestinal Toxicity:Diarrhea

and Colitis

Nursing Assessm

entLook:-


eak?-


eight?-


-D


Grading Toxicity


e, or liquidystools)

Colitis (inflam

mation of the intestinallining)

Listen:-

Quantity &

quality of bowelm

ovements

(e.g., change in/increased frequency over baseline): solid, soft,or liquid diarrhea;dark orbloody stools;or stools that float

-Fever

-A


ping-

Increased fatigue-

Upset stom

ach,nausea,or vomiting

-A


ping-

Bloating/increased gas

-D

ecreased appetite orfood aversions

Recognize:

-S

erum chem


alities-

Infectious vsim

mune-related adverse event

causation-

Peritonealsigns

of bowel perforation (i.e.,


Managem


uidance)

Overall Strategy:

-R


Grade 1 (M

ild)-

May continue im

munotherapy

Diet m


-Institute bland diet;decrease fiber, uncooked fruits/vegetables, red m

eats, fats, dairy, oil, caffeine,alcohol, sugar

Grade 2 (M

oderate)-

Send stool sam

ple forC difficile


parasite -

Imm

unotherapyto be w

ithhelduntil G

rade ≤1 orpatient’sbaseline (ipilim

umab, pem

brolizumab, nivolum

ab)-


odium®

(loperamide)orLom

otil ®


Ifupper orlower G

Isymptom

spersist >5–7 days

oO

ral steroids* to be started (prednisone 0.5m

g–1m

g/kg/day or equivalent)o

After control of sym

ptoms, a ≥4-w

eek steroid* taper will

be initiated-

Imm

unotherapyto

be discontinued ifGrade 2

symptom

spersist≥6 w

eeks (ipilimum

ab)or≥12 w

eeks (pembrolizum

ab,nivolum

ab),or for inability to reduce steroid dose to ≤7.5 mg

(ipilimum

ab) or≤10 m

g prednisone or equivalent(pem

brolizumab, nivolum

ab) within 12 w

eeks

Diet m

odification:-

Institute bland dietlow in fiber, residue,and fat (B

RA

T[B

ananas, Rice, A

pplesauce,Toast] diet)-


eats,fats,dairy, oil,caffeine, alcohol, sugar

-A

void laxativesor stool softeners

-A

dvance diet slowly

assteroids

are tapered,* reduced to lowdoses

and assessfor loose or liquid stoolfor severaldays or

longer-



(Moderate) persistent orrelapsed

symptom

s with steroid*

taper-

Consider gastroenterology consultfor possible intervention


IV steroids*

to be started at1m

g/kg/day-

Imm

unotherapyto

be helduntil≤G

rade 1-

Controlsym

ptoms, then ≥4-w

eeksteroid* taper

-R

ecurrent diarrhea is more likely w

hen treatmentis

restarted

Grades 3-4


Onset: o

Continued dietm

odification, anti-diarrheals,and steroidtitration

-Im

munotherapy:

oG

rade 3: Pembrolizum

abor nivolum

abto be w

ithheld w

hen used as singleagent;ipilim

umab

to be discontinued

as single agent andnivolum

ab when given

with ipilim

umab

oG

rade 4: Ipilimum

ab and/or PD-1 inhibitorto be

discontinued-

Does

of steroids*to

be increased:o

Steroids* 1-2 m

g/kg/day prednisone orequivalent:m


edrol ®)1 g IV(daily

divided)doses

-H

ospitalization-

GI consultation

-A

ssess forperitoneal signs, perforation (NP

O &

abdominalx-

ray, surgical consultprn)-

Use caution w

ith analgesics (opioids) and anti-diarrhealm

edications



steroid* infusion)-

Infliximab

(Rem

icade®)5

mg/kg infusion

may

be considered-

May

require ≥1 infusion to manage sym

ptoms

(may

re-adm

inister at week 2 &

week

6)-

Avoid w

ith bowelperforation or sepsis

-P

PD

(tuberculin)testing not required in this setting -

Infliximab infusion delay m

ay have life-threatening consequences

Diet m

odification:-

Very strict w

ith acute symptom

s:clear liquids;verybland, low

fiberand low residue (B

RA

T diet)-

Advance dietslow

ly as steroids* reduced to low doses

-S

teroids*to be tapered slow


-Supportive

medications

for symptom

atic managem

ent:o

Loperamide:2

capsulesatthe onset &

1 with each

diarrhea stoolthereafter, with a m

aximum

of 6 perdayo

Diphenoxylate/atropine 1-4

tabletsper day

oS

imethicone

when necessary

Grade 1 (M

ild)A

symptom

atic; clinical ordiagnosticobservation only;intervention notindicated

Grade 2 (M

oderate)A

bdominal pain;blood orm

ucus in stoolG


inal pain; change inbow





odynamic


Grade 5 (D

eath)

Nursing Im

plementation:

-C


ent:grade & docum

ent bowel frequency

-E


s-

Grade sym

ptom &

determine level of care and interventions required

-E


ork and office visit if colitis symptom

s aresuspected

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges


ania), increasedappetite,interrupted


-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-termhigh-dose

steroids:-

Considerantim



double dose M/W

/F; single dose if useddaily) or alternative if sulfa-allergic (e.g., atovaquone [M

epron®]1500 m

g podaily)

-C


Avoid


orotherhepatoxins

Grade 1 (M

ild)-


-M


compared

with

baseline

Grade 2 (M

oderate)-

Increase of4–6 stools/day overbaseline

-M

oderate increase of outputinostom

y compared w

ithbaseline

Grade 3 (Severe)

-Increase of≥7 stools/day


-H



youtput

compared

with

baseline-


DLs


-Life-threatening


icnecrosis, toxic

megacolon)

-U


Grade 5 (D

eath)

RED FLAGS:

-Change in gastrointestinal function, decreased appetite

-Bloating, nausea

-M

ore frequent stools, consistency change from loose to liquid

-Abdom

inal pain-

Fever

AD

Ls = activities of daily living; PD

-1=

programm


Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Mucositis Xerostom

ia Page 1 of 2

Care Step Pathw

ay-M

ucositis & Xerostom

ia

Nursing Assessm

entLook:-


fortable?-


ell?-

Difficulty talking?

-Licking lips to m

oisten often?-

Weight loss?

-D

oes the patient appear dehydrated?-

Does the patient have thrush?

Grading Toxicity

Oral M

ucositisD

efinition: A disorder characterized by inflamm

ation of the oral mucosa

Xerostomia (dry m

outh)D

efinition: A disorder characterized by reduced salivary flow in the oralregion

Listen:-

Does the patient report?o

Mouth pain (tongue, gum

s, buccal mucosa)

oM

outh soreso

Difficulty eating

oW

aking during the sleep to sip water

oR

ecent dental-related issueso

Need for dental w

ork (e.g., root canal, toothex traction)

-H

ave symptom

s worsened?

Recognize:

-A

history of mouth sores

-D

oes patient smoke?

-C

oncomitant m

edications associated with causing

dry mouth?

-R

eports of dry mouth often accom

pany mucositis

-O

ther reports of dry mem

branes(e.g., eyes, nasal

passages, vagina)

Managem

ent(Including anticipatory guidance)

Overall Strategy

-Assess for other etiology of m

ucositis or dry mouth:candidiasis;ask patient about new

medications (particularly antihistam

ines), herbals, supplements,

alternative/complem

entary therapies

Grade 1 (M

ild)-

Anticipate im

munotherapy to continue

-A

dvise ongoing basic oral hygiene A

dvise avoidance of hot, spicy, acidicfoods

-A

nticipate possible alternative treatm

ent(s)o

Zinc supplements or0.2%

zincsulfate m

outhwash

oP

robiotics with Lactobacillus

oB

enzydamine

HC

I-

Assess patient&

family

understanding of recomm

endationsand rationaleo


Grade 2 (M

oderate)-

Ipilimum

ab to be withheld for any G

rade 2event (resum

e when G

rade 0/1)-

Imm

unotherapyto

be discontinued forGrade

2events persisting ≥6

(ipilimum

ab)or ≥12 weeks

(pembrolizum

ab, nivolumab)

-A

ssess forSicca

syndrome,Sjӧgren’s

syndrome

-E

ncourage vigilant oral hygiene

Xerostomia:

-A

dvise moistening agents

oS

aliva substituteo

Synthetic

salivao

Oral lubricants

-A

dvise secretagogueso

Nonpharm

acologic

Sugarless gum

S

ugarless hard candies

Natural lem

ono

Pharm

acologic

Pilocarpine

C

evimeline H

CI

Mucositis:

-V

igilantoral hygieneo

Increase frequency of brushing to Q4

hours and atbedtime

oIf unable to tolerate brushing,advise chlorhexidine gluconate 0.12%

or sodiumbicarbonate rinses

1 tsp baking soda in 8 ouncesof w

ateror

½

tsp salt and 2tbsp

sodiumbicarbonate dissolved in 4 cups ofw

ater-

Encourage sips of cool w

ateror crushed ice o

Encourage soft,bland non-acidic foods

oA

nticipatory guidance regarding use ofpharm

acologic agents(as applicable)

A

nalgesics

Gelclair®

, Zilactin®

2% viscous lidocaine applied to

lesions 15 minutes prior to m

eals

2% m

orphine mouthw

ash

0.5% doxepin m

outhwash

“M

iracle Mouthw

ash”:diphenhydram

ine/lidocaine/sim

ethicone

Corticosteroid rinses

Dexam

ethasone oral solutiono

Monitor w

eighto

Monitor hydration status

-N

utrition referralif appropriate


-N

ivolumab to be w

ithheld for first occurrence G

rade 3 event.Imm

unotherapyto be

discontinuedfor any G

rade4 event or fora

Grade 3 event persisting ≥12 w

eeks(ipilim

umab,pem

brolizumab, nivolum

ab)or anyrecurrent G

rade 3 event (pembrolizum

ab,nivolum

ab)-

Anticipate hospitalization ifunable to tolerate

oral solids orliquids-

Unclear role ofsystem

ic corticosteroids-

Anticipate need for supplem

ental nutrition o

Enteral

oP

arenteral-

Anticipatory guidance regarding use of

pharmacologic agents

oA

nalgesics

System

ic opioidsm

ay be indicated -

Oral care

-A

ssesspatient &

family understanding of toxicity

and rationale for interventionsas w

ell astreatm

ent discontinuation o


Grade 1 (M

ild)A

symptom

atic or mild sym

ptoms;

intervention not indicated

Grade 2 (M

oderate)M

oderate pain; not interfering w

ith oral intake; modified diet

indicated

Grade 3 (Severe)

Severe pain; interfering w

ith oral intake


Life-threatening consequences; urgent intervention indicated

Grade 5

(Death)

Grade 1 (M

ild)S

ymptom

atic (e.g.,dry or thick saliva) w

ithout significant dietary alteration; unstim

ulated saliva flow

>0.2 mL/m

in

Grade 2 (M

oderate)M

oderate symptom

s; oral intake alterations (e.g., copious w

ater, other lubricants, diet lim

ited to purees and/or soft, m

oist foods); unstim

ulated saliva 0.1 to 0.2 m

L/min

Grade 3 (Severe)

Inability to adequately aliment

orally; tube feeding or total parenteral nutrition

indicated; unstim

ulated saliva <0.1 mL/m

in



Grade 5

(Death)

Interventions in at-risk patients-

Advise basic oral hygiene:o

Tooth brushing (soft toothbrush,avoid toothpaste w

ith whitening

agents)o

Use ofdental floss daily

o>1 m

outh rinsesto m

aintain oralhygiene (avoid com

mercial

mouthw

ashesor those w

ith alcohol)

-If patient w

ears dentures, assess forproper fit, areas

of irritation,etc.-

Dental referral if necessary

-A

ssess patient& fam

ilyunderstanding of prevention strategies and rationaleo


Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Care Step Pathw

ay-M

ucositis & Xerostom

ia

Nursing Assessm

entLook:-


fortable?-


ell?-

Difficulty talking?

-Licking lips to m

oisten often?-

Weight loss?

-D


Does the patient have thrush?

Grading Toxicity

Oral M

ucositisD

efinition: A disorder characterized by inflamm

ation of the oral mucosa

Xerostom

ia (dry mouth)

Definition: A disorder characterized by reduced salivary flow

in the oralregion

Listen:-

Does the patient report?o

Mouth pain (tongue, gum

s, buccal mucosa)

oM

outh sores o

Difficulty eating

oW

aking during the sleep to sip water

oR

ecent dental-related issueso

Need for dental w

ork (e.g., root canal, tooth extraction)

-H

ave symptom

s worsened?

Recognize:

-A

history of mouth sores

-D

oes patient smoke?

-C

oncomitant m

edications associated with causing

dry mouth?

-R

eports of dry mouth often accom

pany mucositis

-O

ther reports of dry mem

branes(e.g., eyes, nasal

passages, vagina)

Managem

ent(Including anticipatory guidance)

Overall Strategy

-Assess for other etiology of m

ucositis or dry mouth: candidiasis;ask patient about new

medications (particularly antihistam

ines), herbals, supplements,

alternative/complem

entary therapies

Grade 1 (M

ild)-

Anticipate im


-A

dvise ongoing basic oral hygiene A

dvise avoidance of hot, spicy, acidic foods

-A

nticipate possible alternative treatm

ent(s)o

Zinc supplements or 0.2%

zinc sulfate m

outhwash

oP

robiotics with Lactobacillus

oB

enzydamine

HC

I-

Assess patient &

family

understanding of recomm

endations and rationaleo


Grade 2 (M

oderate)-

Ipilimum


rade 2event (resum

e when G

rade 0/1)-

Imm

unotherapy to be discontinued for Grade

2events persisting ≥6

(ipilimum

ab)or ≥12 weeks

(pembrolizum

ab, nivolumab)

-A

ssess for Sicca syndrom

e, Sjӧgren’s syndrom

e -

Encourage vigilant oral hygiene

Xerostomia:

-A

dvise moistening agents

oS

aliva substituteo

Synthetic saliva

oO

ral lubricants -

Advise secretagogues o

Nonpharm

acologic

Sugarless gum

S

ugarless hard candies

Natural lem

ono

Pharm

acologic

Pilocarpine

C

evimeline H

CI

Mucositis:

-V

igilant oral hygieneo

Increase frequency of brushing to Q4

hours and at bedtime

oIf unable to tolerate brushing, advise chlorhexidine gluconate 0.12%

or sodium

bicarbonate rinses

1 tsp baking soda in 8 ounces of water

or

½ tsp salt and 2 tbsp

sodium

bicarbonate dissolved in 4 cups of w

ater-

Encourage sips of cool w

ater or crushed ice o

Encourage soft, bland non-acidic foods

oA

nticipatory guidance regarding use of pharm

acologic agents (as applicable)

Analgesics

Gelclair®

, Zilactin®

2%

viscous lidocaine applied to lesions 15 m

inutes prior to meals

2%

morphine m

outhwash

0.5%

doxepin mouthw

ash

“Miracle M

outhwash”:

diphenhydramine/lidocaine/

simethicone

C

orticosteroid rinses

Dexam

ethasone oral solutiono

Monitor w

eighto

Monitor hydration status

-N

utrition referral if appropriate


-N

ivolumab to be w

ithheld for first occurrence G

rade 3 event. Imm

unotherapyto be

discontinuedfor any G

rade 4 event or for aG

rade 3 event persisting ≥12 weeks

(ipilimum

ab, pembrolizum

ab, nivolumab)or any

recurrent Grade 3 event (pem

brolizumab,

nivolumab)

-A

nticipate hospitalization if unable to tolerate oral solids orliquids

-U

nclear role of systemic corticosteroids

-A

nticipate need for supplemental nutrition

oE

nteral o

Parenteral

-A

nticipatory guidance regarding use of pharm

acologic agents o

Analgesics

System

ic opioids may be indicated

-O

ral care -

Assess patient &

family understanding of toxicity

and rationale for interventions as well as



Grade 1 (M

ild)A

symptom

atic or mild sym

ptoms;

intervention not indicated

Grade 2 (M

oderate)M

oderate pain; not interfering w

ith oral intake; modified diet

indicated

Grade 3 (Severe)

Severe pain; interfering w

ith oral intake



Grade 5

(Death)

Grade 1 (M

ild)S

ymptom

atic (e.g.,dry or thick saliva) w

ithout significant dietary alteration; unstim

ulated saliva flow

>0.2 mL/m

in

Grade 2 (M

oderate)M

oderate symptom

s; oral intake alterations (e.g., copious w

ater, other lubricants, diet lim

ited to purees and/or soft, m

oist foods); unstim

ulated saliva 0.1 to 0.2 m

L/min

Grade 3 (Severe)

Inability to adequately aliment

orally; tube feeding or total parenteral nutrition

indicated; unstim

ulated saliva <0.1 mL/m

in



Grade 5

(Death)

Interventions in at-risk patients-

Advise basic oral hygiene:o

Tooth brushing (soft toothbrush, avoid toothpaste w

ith whitening

agents) o

Use of dental floss daily

o>1 m

outh rinses to maintain oral

hygiene (avoid comm

ercial m

outhwashes or those w

ith alcohol)

-If patient w

ears dentures, assess for proper fit, areas of irritation, etc.

-D

ental referral if necessary -

Assess patient &

family

understanding of prevention strategies and rationaleo


Copyright ©

2017 Melanom


Mucositis Xerostom

ia Page 2 of 2

© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Hepatotoxicity Page 1 of 3

RED FLAGS:

- Severe abdom

inal pain, ascites, somnolence, jaundice, m

ental status changes

Care Step Pathw

ay–

Hepatotoxicity

(imm

unotherapy-induced inflamm

ation of liver tissue)

Nursing Assessm

entLook:-

Does the patient appear fatigued or listless?

-D

oes the patient appear jaundiced?-

Does the patient appear diaphoretic?

-D

oes the patient have any ascites?

Grading Toxicity: U

LN

Listen:-

Change in energy level?

-C

hange in skin color? Yellowing?

-C

hange in stool color (paler)?-

Change in urine color (darker/tea colored)?

-A

bdominal pain:specifically, right upper quadrant pain?

-B

ruising or bleeding more easily?

-Fevers?

-C

hange in mental status?

-Increased sw

eating?

Recognize:

-E

levation in LFTso

AS

T/SG

OT

oA

LT/SG

PT

oB

ilirubin (total/direct)-

Alteration in G

I function-

Sym

ptoms such as abdom

inal pain, ascites, som

nolence, and jaundice-

Other potential causes (viral, drug toxicity,

disease progression)

Managem

ent(including anticipatory guidance)

Overall Strategy:

-LFTs should be checked and results review

ed prior to each dose of imm

unotherapy-

Rule out infectious, non-infectious,and m

alignant causes. Consider assessing for new

onset or re-activation of viral hepatitis, medications (acetam

inophen, statins, and

other hepatotoxic meds, or supplem

ents/herbals), recreational substances (alcohol);consider disease progression

Infliximab infusions are notrecom

mended due to potential hepatotoxic effects

Grade 1 (M

ild)A

ST/A

LT:>U

LN–

3.0×U

LNB

ilirubin: >ULN

–1.5×

ULN

Grade 2 (M

oderate)A

ST/A

LT:>3.0×

–5.0×

ULN

Bilirubin: >1.5×

–3.0×

ULN

Grade 3 (Severe)

AS

T/ALT: >5.0×

–20.0×

ULN

Bilirubin: >3.0 ×

ULN


AS

T/ALT: >20×

ULN

Bilirubin: >10 ×

ULN

Grade 5 (D

eath)

Grade 1 (M

ild)-

Imm

unotherapy may be

withheld if LFTs are trending

upward; recheck LFTs w

ithin ~ 1 w

eek

Grade 3 (Severe)

-S

teroids*to be initiated at 2

mg/kg/day

prednisone or equivalent daily oral -

Nivolum

abto be w

ithheldfor first-occurrence

Grade 3 event. Ipilim

umab to be discontinued

for any Grade 3 event, and nivolum

ab or pem

brolizumab

for any recurrent Grade 3 event

or Grade 3 event persisting ≥12 w

eeks-

Adm

ission for IV steroids*

-R

/O hepatitis infection (acute infection or

reactivation)-

Daily LFTs

-If sustained elevation is significant and/or refractory to steroids* potential forA

DD

ING

to steroid regim

en imm

unosuppressive agent:o

CellC

ept ®(m

ycophenolate mofetil) 500

mg

-1000

mg po q 12 hours

OR

oA

ntithymocyte globulin infusion

-H

epatology/gastroenterology consult-

Consider liver biopsy

-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q

3 days, then w

eekly-

If LFTnorm

alized and symptom

s resolved,steroids* to be tapered over ≥4 w

eeks

Grade 4 (Life-Threatening)

-Im

munotherapy

to be discontinued-

Hospital adm

ission-

Steroids*

to be initiated at2m

g/kg/day prednisone or equivalent daily intravenous

-R

/O hepatitis infection

-D

aily LFTs-

If sustained elevation and refractory to steroids* potential for A

DD

ING

to steroid regim

en:o

CellC

ept ®(m


mg

-1000m

g po or IV q 12 hours

OR

oA


-H




3 days, then weekly

-If LFTs norm

alized and symptom

s resolved,steroids*to be tapered

slowly over ≥4

weeks

Nursing Im

plementation:

-R

eview LFT

results prior to administration of im

munotherapy

-E


s-

Early intervention w

ith lab work and office visit if hepatotoxicity is suspected

-G

rade LFTsand

any other accompanying sym

ptoms

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-term

high-dosesteroids:

-C

onsiderantimicrobialprophylaxis

(sulfamethoxazole/trim

ethoprim double dose M

/W/F; single dose if used

daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron

®]1500 mg po daily)

-C

onsideradditionalantiviraland antifu ngalcoverage-

Avoid


orotherhepatoxins

Grade 2 (M

oderate)-

Imm

unotherapyto be w

ithheld; recheck LFTs daily x 3 days or every 3 days;to be resum

edw

hen complete/partial resolution

of adverse reaction (Grade 0/1)

-Im

munotherapy to be discontinued for

Grade 2 events lasting ≥6

(ipilimum

ab) or ≥12

weeks

(pembrolizum

ab, nivolumab),

orforinability to reduce steroid dose to 7.5 m

g prednisone or equivalent per day -

Consider starting steroids* 0.5

mg

–1

mg/kg/day prednisone or equivalent daily

(IV m

ethylprednisolone 125m

g total daily dose) +

an anti-acid-

Considerhospitaladm

ission for IV

steroids*-

If LFT normalized and sym

ptoms

resolved, steroids*to be tapered

over ≥ 4 w

eeksw

hen function recovers-

Once patientreturns to baseline or G

rade 0-1,consider resum

ing treatment

ALT

=alanine am

inotransferase; AS

T=

aspartate aminotransferase; G

I=gastrointestinal;LFT

-liver function test; SG

OT

-serum glutam

ic oxaloacetic transaminase; S

GP

T=

serum glutam

ic pyruvic transam

inase; ULN

=upper lim

it of normal

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org


RED FLAGS:

- Severe abdom



Care Step Pathw

ay–

Hepatotoxicity

(imm



Nursing Assessm

entLook:-


-D



-D


Grading Toxicity: U

LN

Listen:-


-C


-C



-A


-B


-Fevers?

-C


-Increased sw

eating?

Recognize:

-E

levation in LFTso

AS

T/SG

OT

oA

LT/SG

PT

oB


Alteration in G

I function-

Sym

ptoms such as abdom





Managem


Overall Strategy:



unotherapy-









Grade 1 (M

ild)A

ST/A

LT:>U

LN–

3.0×U

LNB

ilirubin: >ULN

–1.5×

ULN

Grade 2 (M

oderate)A

ST/A

LT:>3.0×

–5.0×

ULN

Bilirubin: >1.5×

–3.0×

ULN

Grade 3 (Severe)

AS

T/ALT: >5.0×

–20.0×

ULN

Bilirubin: >3.0 ×

ULN


AS

T/ALT: >20×

ULN

Bilirubin: >10 ×

ULN

Grade 5 (D

eath)

Grade 1 (M

ild)-

Imm

unotherapy may be



ithin ~ 1 w

eek

Grade 3 (Severe)

-S


mg/kg/day


Nivolum

abto be w





ab or pem

brolizumab



eeks-

Adm


-R


reactivation)-

Daily LFTs


DD

ING

to steroid regim

en imm


CellC

ept ®(m


mg

-1000

mg po q 12 hours

OR

oA


-H




3 days, then w

eekly-

If LFTnorm

alized and symptom


eeks


-Im

munotherapy

to be discontinued-

Hospital adm

ission-

Steroids*



-R


-D

aily LFTs-


DD

ING

to steroid regim

en:o

CellC

ept ®(m


mg

-1000m


OR

oA


-H




3 days, then weekly

-If LFTs norm

alized and symptom


slowly over ≥4

weeks

Nursing Im

plementation:

-R

eview LFT


munotherapy

-E


s-



-G

rade LFTsand


ptoms

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-term

high-dosesteroids:

-C







-C

onsideradditionalantiviraland antifu ngalcoverage-

Avoid


orotherhepatoxins

Grade 2 (M

oderate)-

Imm

unotherapyto be w


edw



-Im



(ipilimum

ab) or ≥12

weeks

(pembrolizum

ab, nivolumab),




mg

–1


(IV m



an anti-acid-

Considerhospitaladm

ission for IV

steroids*-


ptoms


over ≥ 4 w

eeksw




ing treatment

ALT

=alanine am

inotransferase; AS

T=




OT

-serum glutam


GP

T=

serum glutam

ic pyruvic transam

inase; ULN

=upper lim

it of normal

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org


RED FLAGS:

- Severe abdom



Care Step Pathw

ay–

Hepatotoxicity

(imm



Nursing Assessm

entLook:-


-D



-D


Grading Toxicity: U

LN

Listen:-


-C


-C



-A


-B


-Fevers?

-C


-Increased sw

eating?

Recognize:

-E

levation in LFTso

AS

T/SG

OT

oA

LT/SG

PT

oB


Alteration in G

I function-

Sym

ptoms such as abdom





Managem


Overall Strategy:



unotherapy-









Grade 1 (M

ild)A

ST/A

LT:>U

LN–

3.0×U

LNB

ilirubin: >ULN

–1.5×

ULN

Grade 2 (M

oderate)A

ST/A

LT:>3.0×

–5.0×

ULN

Bilirubin: >1.5×

–3.0×

ULN

Grade 3 (Severe)

AS

T/ALT: >5.0×

–20.0×

ULN

Bilirubin: >3.0 ×

ULN


AS

T/ALT: >20×

ULN

Bilirubin: >10 ×

ULN

Grade 5 (D

eath)

Grade 1 (M

ild)-

Imm

unotherapy may be



ithin ~ 1 w

eek

Grade 3 (Severe)

-S


mg/kg/day


Nivolum

abto be w





ab or pem

brolizumab



eeks-

Adm


-R


reactivation)-

Daily LFTs


DD

ING

to steroid regim

en imm


CellC

ept ®(m


mg

-1000

mg po q 12 hours

OR

oA


-H




3 days, then w

eekly-

If LFTnorm

alized and symptom


eeks


-Im

munotherapy

to be discontinued-

Hospital adm

ission-

Steroids*



-R


-D

aily LFTs-


DD

ING

to steroid regim

en:o

CellC

ept ®(m


mg

-1000m


OR

oA


-H




3 days, then weekly

-If LFTs norm

alized and symptom


slowly over ≥4

weeks

Nursing Im

plementation:

-R

eview LFT


munotherapy

-E


s-



-G

rade LFTsand


ptoms

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-term

high-dosesteroids:

-C







-C


Avoid


orotherhepatoxins

Grade 2 (M

oderate)-

Imm

unotherapyto be w


edw



-Im



(ipilimum

ab) or ≥12

weeks

(pembrolizum

ab, nivolumab),




mg

–1


(IV m



an anti-acid-

Considerhospitaladm

ission for IV

steroids*-


ptoms


over ≥ 4 w

eeksw




ing treatment

ALT

=alanine am

inotransferase; AS

T=




OT

-serum glutam


GP

T=

serum glutam

ic pyruvic transam

inase; ULN

=upper lim

it of normal

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Hypophysitis Page 1 of 2

Nursing Assessm

ent

Care Step Pathw

ay –H

ypophysitis(inflam

mation of the pituitary gland)

Look:-

Does the patient appear fatigued?

-D

oes the patient look listless?-

Does the patient look ill?

-D

oes the patient look uncomfortable?

Grading Toxicity (O

verall)

Listen:-

Does the patient report:o

Change in energy?

oH

eadache?o

Dizziness?

oN

ausea/vomiting?

oA

ltered mental status?

oV

isual disturbances?o

Fever?

Recognize:

-Low

levels of hormones produced by pituitary gland

( AC

TH, TS

H, FS

H, LH

, GH

, prolactin)-

Brain M

RI w

ith pituitary cuts: enhancement and

s welling of the pituitary gland.

-D

DX adrenal Insufficiency: low

cortisol and highA

CTH

-D

DX prim

ary hypothyroidism: low

free T4 and hi ghTS

H

Managem

ent

Overall Strategy:

-Ipilim

umab to be w

ithheld for any symptom

atic hypophysitis and discontinued for symptom

atic reactions persisting ≥6 weeks or for inability to reduce steroid dose to

≤7.5 mg prednisone or equivalent per day

-N

ivolumab to be w

ithheld for Grade 2/3 hypophysitis and discontinued for G

rade 4 hypophysitis. Pembrolizum

abto be w

ithheld for Grade 2 hypophysitis and w

ithheld ordiscontinued for G

rade 3/4 hypophysitis-

1m

g/kg methylprednisolone (or equivalent) IV to be given daily

oIf given during acute phase, m

ay reverse inflamm

atory process-

To be followed w

ith prednisone 1-2m

g/kg daily with gradual tapering over at least 4 w

eeks-

Long-term supplem

entation of affected hormones is often required

oSecondary hypothyroidism

requiring levothyroxine replacement

oSecondary hypoadrenalism

requiring replacement hydrocortisone

Typical dose: 20 m

g qAM and 10 m

g qPM-

Assess risk of opportunistic infection based on duration of steroid taper (and consider prophylaxis if needed)-

Collaborative m

anagement approach w

ith endocrinology (particularly if permanent loss of organ function)

Grade 1 (M

ild)A

symptom

atic or mild sym

ptoms;

clinical or diagnostic observation only (headache, fatigue)

Grade 2 (M

oderate)M

oderate symptom

s;limiting age-

appropriate instrumental A

DLs

(headache, fatigue)

Grade 3 (Severe)

Severe or m

edically significant sym

ptoms; lim

iting self-care ADL

(sepsis, severe ataxia)


Urgent intervention required (sepsis, severe

ataxia)

Grade 5 (D

eath)

Nursing Im

plementation:

-A

CTH

and thyroid panel should be checked at baseline and prior to each dose ofipilimum

ab-

Ensure that M

RI is ordered w

ith pituitary cuts or via pituitaryprotocol

-A

nticipate treatment w

ith corticosteroid and imm

unotherapy hold-

Review

proper administration of steroid

oTake w

ith food o

Take in AM

-E

ducate patient regarding possibility of permanent loss of organ function (pituitary; possibly others

if involved [thyroid, adrenal glands])-

Sick-day instructions, vaccinations,etc

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-termhigh-dose

steroids:-

Considerantim



double dose M/W

/F;single dose ifuseddaily) or alternative ifsulfa-allergic (e.g.,atovaquone [M

epron®]1500 m

g podaily)

-C


Avoid


orotherhepatoxins

AC

TH = adrenocorticotropic horm

one; AD

Ls = activities ofdaily living; DD

X = differentialdiagnosis; FSH

= follicle-stimulating horm

one; GH

= growth horm

one; LH =

luteinizing hormone; M

RI =

magnetic resonance im

aging;TSH

= thyroid stimulating horm

one.

RED FLAGS:

-Sym

ptoms of adrenal insufficiency

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Hypophysitis Page 2 of 2

Nursing Assessm

ent

Care Step Pathw

ay–

Hypophysitis

(inflamm

ation of thepituitary

gland)

Look:-


-D

oes the patient looklistless?

-D

oes the patient lookill?

-D

oes the patient lookuncom

fortable?

Grading Toxicity (O

verall)

Listen:-

Does the patientreport:o

Change in energy?

oH

eadache?o

Dizziness?

oN

ausea/vomiting?

oA

ltered mental status?

oV

isual disturbances?o

Fever?

Recognize:

-Low

levels of hormones produced by pituitary

gland (A

CTH

, TSH

, FSH

, LH, G

H, prolactin)

-B

rain MR

I with pituitary

cuts: enhancementand

swelling of the pituitary gland.

-D

DX adrenal Insufficiency: low

cortisol and high A

CTH

-D

DX prim

ary hypothyroidism: low

free T4 and high TS

H

Managem

ent

Overall Strategy:

-Ipilim

umab to be

withheld for any sym

ptomatic hypophysitis

and discontinued for symptom

atic reactionspersisting ≥6 w

eeks or for inability to reduce steroid dose to≤7.5 m

g prednisone or equivalent per day-

Nivolum

ab to be withheld for G

rade 2/3 hypophysitis and discontinued for Grade 4 hypophysitis.Pem

brolizumab

to be withheld for G

rade 2 hypophysitis and withheld or

discontinued for Grade 3/4 hypophysitis

-1

mg/kg m

ethylprednisolone (or equivalent)IV to be given dailyo

If given during acute phase, may reverse inflam

matory process

-To be follow

ed with

prednisone 1-2m

g/kg dailyw

ith gradual tapering overat least4 weeks

-Long-term

supplementation of affected horm

ones is often requiredo

Secondary hypothyroidismrequiring levothyroxine

replacement

oSecondary

hypoadrenalism requiring replacem

ent hydrocortisone

Typical dose:20 mg qAM

and 10 mg qPM

-Assess risk of opportunistic infection based on duration of steroid taper (and consider prophylaxis if needed)

-C

ollaborative managem

ent approach with endocrinology

(particularly if permanentloss of organ function)

Grade 1 (M

ild)A

symptom

atic or mild

symptom

s;clinical or diagnostic observation only (headache, fatigue)

Grade 2

(Moderate)

Moderate sym

ptoms;lim

iting age-appropriate instrum

ental AD

Ls(headache, fatigue)

Grade 3 (Severe)

Severe or m

edically significantsym

ptoms;lim

iting self-care ADL

(sepsis, severe ataxia)


Urgent intervention required (sepsis, severe

ataxia)

Grade 5 (D

eath)

Nursing Im

plementation:

-A

CTH

and thyroid panel should be checked at baseline and prior to each dose of ipilimum

ab-

Ensure that M

RI is ordered w

ith pituitary cuts or via pituitary protocol-

Anticipate treatm

ent with corticosteroid and im

munotherapy hold

-R

eview proper adm

inistration of steroido

Take with food

oTake in A

M-

Educate patient regarding possibility of perm

anent loss of organ function (pituitary; possibly others if involved [thyroid, adrenal glands])-

Sick-day instructions, vaccinations, etc

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-termhigh-dose

steroids:-

Considerantim



double dose M/W

/F; single dose if useddaily) or alternative if sulfa-allergic (e.g., atovaquone [M

epron®]1500 m

g po daily)-

Consideradditionalantiviraland antifungalcoverage

-A

voidalcohol/acetam

inophenorotherhepatoxins

AC

TH = adrenocorticotropic horm

one; AD

Ls = activities of daily living; DD

X = differential diagnosis; FSH

= follicle-stimulating horm

one; GH

= growth horm

one; LH = luteinizing horm

one; MR

I = m

agnetic resonance imaging; TS

H= thyroid stim

ulating hormone.

RED FLAGS:

-Sym

ptoms of adrenal insufficiency

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Thyroiditis Page 1 of 2

Care Step Pathw

ay –Thyroiditis

(inflamm

ation of the thyroid gland)

Nursing Assessm

entLook:-


ell?-

Changes in w

eight since last visito

Appear heavier? Thinner?

-C

hanges in hair texture/thickness?-

Appearing hot/cold?

-D

oes the patient look fatigued?

Type of Thyroid Abnorm

ality

Listen:-

Appetite/weight changes?

-H

ot or cold intolerance?-

Change in energy.m

ood, or behavior?-

Palpitations?-

Increased fatigue?-

Bowel-related changes?

oC

onstipation/diarrhea-

Skin-related changes?o

Dry/oily

Recognize:

-E

nsure that patient undergoesthyroid function

testsprior to first dose,every 12 w

eeks while on

PD

-1therapy

and q3 weeks w

ith ipilimum

ab-

High TS

H w

ith low free T4 consistent w

ithprim

ary hypothyroidism-

DD

X: secondary hypothyroidism due t o

hypophysitis, low TS

H and low

free T4-

Occasionally thyroiditis w

ith transienthyperthyroidism

(low TS

H and high free T4)

may be follow

ed by more longstanding

hypothyroidism (high TS

H and low

free T4)-

Other im

mune-related toxicity?

-P

rior thyroid dysfunction?

Managem

ent

TSH>5, <10

mIU

/Lw

ithnorm

al free T4, T3R

epeat TFTs in 4–6 weeks

TSH >10 w

ith normal or low

free T4 & T3

-B

egin thyroid replacement if

symptom

atic-

May consider repeating levels

in 2-4 w

eeks ifasymptom

atic-

Levothyroxine dose 1.6m

cgper

weight (kg)or 75–100

mcg daily

-R

epeat TSH

in 4–6 weeks and

titrate dose to reference rangeTS

H

TSH low

or <0.01 mIU

/Lw

ith high freeT4 or T3-

Considerradioactive iodine therapy

orm

ethimazole treatm

ent-

Consider use of beta blockers

forsym

ptomatic patients (e.g., for tachycardia or

murm

ur)

TSH low

or <0.01 mIU

/Lw

ith norm

al or high free T3 or T4-

Acute thyroiditis

-R

arely Graves’-like disease

TSH>5, <10 m

IU/L

with norm

al free T4, T3S

ubclinical hypothyroidism

TSH >10 m

IU/L

with norm

al or low

free T4 & T3

Prim

ary hypothyroidism

TSH low

or <0.01m

IU/L

with high free T4

or T3H

yperthyroidism

TSH low

or <0.01m

IU/L

with

normal or high free T3 or T4

-C

onsidermeasuring anti-thyroid

antibodies and/or TSH

-receptorautoantibodies (TR

AB

)to establish autoim

mune etiology

-If patienthas not received IV iodinated contrast w

ithin 2 months, can consider

a diagnostic thyroid uptake & scan

-A

cute thyroiditis usually resolves orprogresses to hypothyroidism

;thus,can repeat TFTs in 4–6 w

eeks-

If TRA

B high, obtain a thyroid uptake

scan&

refer to endocrinology-

Short period of 1

mg/kg prednisone or

equivalent may

be helpfulin acute thyroiditis

-C

onsider use of beta blockersand

imm

unotherapyhold forsym

ptomatic

patients(e.g.,beta blockers for

tachycardia/murm

ur and im

munotherapy

holds for patientsw

ho have acute thyroiditis threatening an airw

ay). Therapy is often restarted w

hen symptom

s are mild/tolerable

Nursing Im

plementation:

-Educate patient that hypothyroidism

is generally not reversible-

Assessm

edication compliance w

ith oral thyroid replacement or suppression

-H

istoryof thyroid disorders does not increase ordecrease risk of incidence

-C

onsider collaborative managem

entwith endocrinologist,especially

if the patientis hyperthyroid, particularly if a thyroid scan is needed

RED FLAGS:

-Sw

elling of thyroid gland causingcom

promised airw

ay

DD

X = differentialdiagnosis; PD-1 = program

med celldeath protein 1; TFT = thyroid function test; TS

H = thyroid stim

ulating hormone

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2017 Melanom


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elanoma N


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elanomanurse.org

Thyroiditis Page 2 of 2

Care Step Pathw

ay–

Thyroiditis(inflam

mation of the thyroid gland)

Nursing Assessm

entLook:-


ell?-

Changes in w

eightsince last visito

Appear heavier? Thinner?

-C

hanges in hair texture/thickness?-

Appearing hot/cold?

-D

oes the patient lookfatigued?

Type of Thyroid Abnorm

ality

Listen:-

Appetite/weightchanges?

-H

ot or cold intolerance?-

Change in energy.m

ood, or behavior?-

Palpitations?-

Increased fatigue?-

Bowel-related changes?

oC

onstipation/diarrhea-

Skin-related changes?o

Dry/oily

Recognize:

-E

nsure thatpatient undergoesthyroid function

testsprior to first dose,every 12 w

eeks while on

PD

-1therapy

and q3 weeks w

ith ipilimum

ab-

High TS

H w

ith low free T4 consistent w

ith prim

ary hypothyroidism-

DD

X: secondary hypothyroidism due to

hypophysitis, low TS

H and low

free T4-

Occasionally thyroiditis w

ith transienthyperthyroidism

(low TS

H and high free T4)

may be follow

ed by more longstanding

hypothyroidism (high TS

H and low

free T4)-

Other im

mune-related toxicity?

-P

rior thyroid dysfunction?

Managem

ent

TSH>5, <10 m

IU/L

with

normal free T4, T3

Repeat TFTs in 4–6 w

eeks

TSH >10 w

ith normal or low

free T4 &

T3-

Begin thyroid replacem

ent ifsym

ptomatic

-M

ay consider repeating levels i n2- 4 w

eeks if asymptom

atic-

Levothyroxine dose 1.6m

cg perw

eight (kg) or 75–100m

cg daily-

Repeat TS

H in 4–6 w

eeks andtitrate dose to reference rangeTS

H

TSH low

or <0.01 mIU

/Lw

ith high free T4 or T3-

Consider radioactive iodine therapy or

methim

azole treatment

-C

onsider use of beta blockers forsym

ptomatic patients (e.g., for tachycardia or

murm

ur)

TSH low

or <0.01 mIU

/Lw

ithnorm

al or high free T3 or T4-

Acute thyroiditis

-R

arely Graves’-like disease

TSH>5, <10

mIU

/Lw

ith normal

free T4, T3S

ubclinical hypothyroidism

TSH >10 m

IU/L

with norm

al or lowfree T4 &

T3P

rimary hypothyroidism

TSH low

or <0.01m

IU/L

with high free T4

or T3H

yperthyroidism

TSH low

or <0.01m

IU/L

with

normal or high free T3 or T4

-C

onsider measuring anti-thyroid

antibodies and/or TSH

-receptorautoantibodies (TR

AB

)to establishautoim

mune etiology

-If patient has not received IV iodinatedc ontrast w

ithin 2 months, can consider

a diagnostic thyroid uptake & scan

-A

cute thyroiditis usually resolves orprogresses to hypothyroidism

; thus,can repeat TFTs in 4–6 w

eeks-

If TRA

B high, obtain a thyroid uptak e

sca n&

refer to endocrinology-

Short period of 1

mg/kg prednisone or

equivalent may be helpful in acute

thyroiditis-

Consider use of beta blockers and

imm

unotherapyhold for sym

ptomatic

patients(e.g.,beta blockers for

tachycardia/murm

ur andim

munotherapy

holds for patientsw

hohave acute thyroiditis threatening anairw

ay). Therapy is often restart edw

hen symptom

s are mild/tolerable

Nursing Im

plementation:

-Educate patient that hypothyroidism

is generally not reversible-

Assess medication com

pliance with oral thyroid replacem

ent or suppression-

History of thyroid disorders does not increase or decrease risk of incidence

-C

onsider collaborative managem

ent with endocrinologist,especially if the patient is hyperthyroid, particularly if a thyroid scan is needed

RED FLAGS:

-Sw

elling of thyroid gland causing comprom

ised airway

DD

X = differential diagnosis; PD-1 = program

med cell death protein 1; TFT = thyroid function test; TS

H = thyroid stim

ulating hormone

Copyright ©

2017 Melanom


Care Step Pathw

ay -Type 1 Diabetes

Mellitus

(imm

une destruction of beta cells in pancreas)

Nursing Assessm

ent

Look:-


-D


Does the breath have a sw

eet/fruity smell?

-Is the patient tachycardic?

Grading Toxicity (B

ased on Fasting Glucose)

Listen:-

Frequent urination?-

Increased thirst?-

Increased hunger?-

Increased fatigue?-

Altered level of consciousness w

ith advanced cases

Recognize:

-S

ymptom

s of diabetes-

Serum

glucose levels-

Other im

mune-related toxicity

-Infections

Managem

entO

verall Strategy: -

Imm

unotherapym

ay be withheld until blood glucose is regulated

-Insulin therapy

-H

ydration-

Endocrine consult

Grade 1 (M

ild)Fasting glucose value >U

LN–

160m

g/dL

Grade 2 (M

oderate)Fasting glucose value >160

–250 m

g/dL

Grade 3 (Severe)

Fasting glucose value >250–

500m

g/dL, hospitalization indicated


Fasting glucose value >500 mg/dL, life-

threatening consequences

Grade 5 (D

eath)

Nursing Im

plementation:

-D

iscuss that DM

1 will likely be perm

anent-

Review

signs andsym

ptoms of hyper/hypoglycem

ia-

Follow patients closely w

ith checks on blood glucose levels, fruity breath, and other symptom

s (e.g.,increased infections)-

Assure early intervention

-P

rovide insulin education (orrefer)-

Discuss possibility of other im

mune-related A

Es, including others of endocrine origin

DM

=diabetes m

ellitus;ULN

=upper lim

it of normal

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w.them

elanomanurse.org

Type 1 Diabetes M

ellitus Page 1 of 1

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elanoma N


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elanomanurse.org

Pneumonitis Page 2 of 2

Care Step Pathw

ay –Pneum

onitis(inflam

mation of lung alveoli)

Nursing Assessm

ent

Look:-


fortable?-

Did the patient have difficulty w

alking to the examroom

?O

r going up stairs?-

Does the patient appear short of breath?

-Is the patient tachypneic?

-D

oes the patient appear to be in respiratory distress?

Grading Toxicity

Pneumonitis

Definition: A

disorder characterized by inflamm

ation focally or diffusely affecting the lung parenchyma

H ypoxia D

efinition: A disorder characterized by decrease in the level of oxygen to the body

Listen:-

Has the patient noted any change in breathing?

-D

oes the patient feel short of breath?-

Does the patient note new

dyspnea on exertion?-

Does the patient notice a new

cough? Or a change in an

ex isting cough?-

Have sym

ptoms w

orsened?-

Are sym

ptoms lim

iting AD

Ls?-

Associated sym

ptoms ?

oFatig ue

oW

heezing

Recognize:

-Is the pulse oxim

etry low? Is it low

er than baselineor

compared w

ithlast visit?

Is it low on exertion?

-Is there a pre-existing pulm

onary autoimm

une conditi on(i.e.,sarcoidosis)?

-Is there a history of prior respiratory com

promise

(e.g.,asthm

a, CO

PD

,congestive heart failure)?-

Has the patient experienced other im

mune-related

adverse effects?

Managem

ent

Overall Strategy:

-Assess for other etiologies

such as infection, pulmonary

embolism

, progressive lung metastases,or lung disease

-Early

intervention to maintain orim

prove physical function and impact on Q

OL

-Assess pulse oxim

etry (resting & on exertion)at baseline and at each visit to assist in identifying a decrease at earlyonset.

Grade 1 (M

ild)-

Anticipate im


-C

ontinue to monitor via radiology

testing(q 2–4

weeks, as needed)

-R

eview sym

ptoms to w

atch for with

patient and family,and rem

ember to

assess atevery subsequent visit

Grade 2 (M

oderate)-

Imm

unotherapyto be w

ithheldfor G

rade 2events (resum

e when G

rade 0/1)-

Imm

unotherapyto

be discontinued forrecurrent (pem

brolizumab, nivolum

ab) orpersistent G

rade 2 events (ipilimum

ab,pem

brolizumab, nivolum

ab)-

Anticipate treatm

ent with:

oC

orticosteroids(e.g.,prednisone 1–2

mg/kg/day

or equivalent)until sym

ptoms

improve to baseline,and

then slowtaper overat least1

month

oIf sym

ptoms do not im

prove within 48–

72 hours, corticosteroiddose w

illbe escalated. IV corticosteroids m

aybe

consideredo

Additional supportive care m

edicationsm

ay also be initiated -

Anticipatory guidance on proper

administration

-A

nticipate the use ofempiric antibiotics until

infection is excluded-

Anticipate that bronchoscopy m

aybe

ordered by provider-

Assess

patient &fam

ily understanding ofrecom


-Identify barriers to adherence

Grades 3–4 (Severe or Life-Threatening)

-D

iscontinue imm

unotherapy for Grade 3/4

events-

Patient w

ill likely need to be admitted to the

hospital for furthermanagem

ent andsupportive care

-A

nticipate the use ofhigh-dose IV

corticosteroids (e.g.,methylprednisolone 2–4

mg/kg/day

or equivalent)-

Once sym

ptoms

have resolved to baseline orG

rade 1, convertto equivalent oralcorticosteroid dose and then taperslow

lyover at least 1 m

onth-

Anticipate the use ofem

piric antibiotics untilinfection is excluded

-A

nticipate the use ofadditionalim

munosuppressive agents

if symptom

s donot im

prove in 48–72 hours(e.g.,inflixim

ab,m

ycophenolate, cyclophosphamide)

-A

ssesspatient &


toxicity and rationale for treatment

discontinuation-

Identify barriers to adherence,specificallycom

pliance with m

edication, physical activity

Grade 1 (M

ild)A

symptom

atic;clinical or diagnostic observations only; intervention not indicated

Grade 2 (M

oderate)S

ymptom

atic; medical intervention

indicated; limiting instrum

ental A

DLs

Grade 3 (Severe)

Severe sym

ptoms; lim

iting self-care A

DLs; oxygen indicated


Life-threatening respiratory comprom

ise; urgent intervention indicated (tracheostom

y, intubation)

Grade 5

(Death)

Grade 1 (M

ild)G

rade 2 (Moderate)

Decreased

oxygen saturation with

exercise (e.g.,pulse ox <88%);

intermittent supplem

ental oxygen

Grade 3 (Severe)

Decreased

oxygen saturation at rest (e.g.,pulse ox <88%

)


Life-threatening airway com

promise; urgent

intervention indicated (tracheostomy,

intubation)

Grade 5

(Death)

Prevention-

No know

n interventions

Nursing Im

plementation:

-Identify high-risk

individuals(e.g.,asthm

a, CO

PD)and those w

ith cardiopulmonary sym

ptoms prior to initiating im

munotherapy. Establish a thorough baseline

-Educate patients thatnew

pulmonary sym

ptoms

should be reported imm

ediately-

Anticipate thatthe steroid requirements to m

anage pneumonitis are high (1 –4

mg/kg/day)and patientw

ill be on corticosteroid therapy for at least 1m

onth-

Educate patients and family

about the rationale for discontinuation of imm

unotherapy inpatients w

hodo develop

moderate or severe pneum

onitis

RED FLAGS:

-Risk of acute onset

-Risk of m

ortality ifpneumonitistreatm

ent isdelayed-

Risk of pneumonitis is greater in patientsreceiving

combination im

munotherapy

regimens

Copyright ©

2017 Melanom


AD

L = activities of daily living;CO

PD

= chronic obstructive pulmonary disease

© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Pneumonitis Page 2 of 2

Care Step Pathw

ay –Pneum

onitis(inflam

mation of lung alveoli)

Nursing Assessm

ent

Look:-


fortable?-

Did the patient have difficulty w

alking to the exam

room?

Or going up stairs?

-D

oes the patient appear short of breath?-

Is the patient tachypneic?-

Does the patient appear to be in respiratory distress?

Grading Toxicity

Pneumonitis

Definition: A

disorder characterized by inflamm

ation focally or diffusely affecting the lung parenchyma

Hypoxia

Definition: A disorder characterized by decrease in the level of oxygen to the body

Listen:-

Has the patient noted any change in breathing?

-D

oes the patient feel short of breath?-

Does the patient note new

dyspnea on exertion?-

Does the patient notice a new

cough? Or a change in an

existing cough?-

Have sym

ptoms w

orsened? -

Are sym

ptoms lim

iting AD

Ls?-

Associated sym

ptoms?

oFatigue

oW

heezing

Recognize:

-Is the pulse oxim

etry low? Is it low

er than baselineor

compared w

ithlast visit?

Is it low on exertion?

-Is there a pre-existing pulm

onary autoimm

une condition (i.e.,sarcoidosis)?

-Is there a history of prior respiratory com

promise

(e.g.,asthm

a, CO

PD

,congestive heart failure)?-

Has the patient experienced other im

mune-related

adverse effects?

Managem

ent

Overall Strategy:

-Assess for other etiologies such as infection, pulm

onary embolism

, progressive lung metastases,or lung disease

-Early intervention to m

aintain or improve physical function and im

pact on QO

L-

Assess pulse oximetry (resting & on exertion) at baseline and at each visit to assist in identifying a decrease at early onset.

Grade 1 (M

ild)-

Anticipate im


-C

ontinue to monitor via radiology

testing(q 2–4

weeks, as needed)

-R

eview sym

ptoms to w

atch for with

patient and family,and rem

ember to

assess at every subsequent visit

Grade 2 (M

oderate)-

Imm

unotherapyto be w

ithheldfor G

rade 2events (resum

e when G

rade 0/1)-

Imm

unotherapy to be discontinued for recurrent (pem

brolizumab, nivolum

ab) or persistent G

rade 2 events (ipilimum

ab, pem

brolizumab, nivolum

ab)-

Anticipate treatm

ent with:

oC

orticosteroids (e.g.,prednisone 1–2m

g/kg/dayor equivalent)until

symptom

sim

prove to baseline,andthen slow

taper over at least 1m

ontho

If symptom

s do not improve w

ithin 48–72 hours, corticosteroid

dose will be

escalated. IV corticosteroids may be

consideredo

Additional supportive care m

edications m

ay also be initiated -


administration

-A

nticipate the use of empiric antibiotics until


Anticipate that bronchoscopy m

ay be ordered by provider

-A

ssess patient & fam

ily understanding of recom



Grades 3–4 (Severe or Life-Threatening)

-D

iscontinue imm

unotherapy for Grade 3/4

events-

Patient w

ill likely need to be admitted to the

hospital for furthermanagem

ent and supportive care

-A

nticipate the use of high-dose IV

corticosteroids (e.g.,methylprednisolone 2–4

mg/kg/day

or equivalent)-

Once sym

ptoms have resolved to baseline or

Grade 1, convert to equivalent oral

corticosteroid dose and then taper slowly

over at least 1 month

-A

nticipate the use of empiric antibiotics until


Anticipate the use of additional

imm

unosuppressive agents if symptom

s donot im

prove in 48–72 hours(e.g.,inflixim

ab, m

ycophenolate, cyclophosphamide)

-A

ssess patient & fam

ily understanding of toxicity and rationale for treatm

ent discontinuation

-Identify barriers to adherence, specifically com

pliance with m

edication, physical activity

Grade 1 (M

ild)A

symptom

atic;clinical or diagnostic observations only; intervention not indicated

Grade 2 (M

oderate)S

ymptom

atic; medical intervention

indicated; limiting instrum

ental A

DLs

Grade 3 (Severe)

Severe sym

ptoms; lim

iting self-care A

DLs; oxygen indicated


Life-threatening respiratory comprom

ise; urgent intervention indicated (tracheostom

y, intubation)

Grade 5

(Death)

Grade 1 (M

ild)G

rade 2 (Moderate)

Decreased

oxygen saturation with

exercise (e.g.,pulse ox <88%);

intermittent supplem

ental oxygen

Grade 3 (Severe)

Decreased

oxygen saturation at rest (e.g.,pulse ox <88%

)


Life-threatening airway com

promise; urgent

intervention indicated (tracheostomy,

intubation)

Grade 5

(Death)

Prevention-

No know

n interventions

Nursing Im

plementation:

-Identify high-risk

individuals(e.g., asthm

a, CO

PD)and those w

ith cardiopulmonary sym

ptoms prior to initiating im

munotherapy. Establish a thorough baseline

-Educate patients that new

pulmonary sym

ptoms should be reported im

mediately

-Anticipate that the steroid requirem

ents to manage pneum

onitis are high (1 –4m

g/kg/day) and patient will be on corticosteroid therapy for at least 1

month

-Educate patients and fam

ily about the rationale for discontinuation of imm

unotherapy in patients who do develop

moderate or severe pneum

onitis

RED FLAGS:


-Risk of m

ortality if pneumonitis treatm

ent is delayed -

Risk of pneumonitis is greater in patients receiving com

bination imm

unotherapy regimens

Copyright ©

2017 Melanom


AD

L = activities of daily living; CO

PD

= chronic obstructive pulmonary disease

© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Arthralgias and A

rthritis Page 1 of 3

Care Step Pathw

ay-Arthralgias and Arthritis

Nursing Assessm

entLook:-


fortable?-


ell?-

Is their gait affected?-

Obvious sw

ollen, or deformed joint(s)?

-Is the patient having trouble getting up and dow

nstairs?

Grading Toxicity

Arthralgia

Definition: A

disorder characterized by a sensation of marked discom

fort in a joint

Arthritis

Definition: A disorder characterized by inflam

mation involving a joint

Listen:-

Have sym

ptoms w

orsened?-

Are sym

ptoms lim

iting AD

Ls?-

Are sym

ptoms increasing the patient’s risk for

fall? Other safety issues?

-A

ssociated symptom

s?o

Fatigue (new or w

orsening)

Recognize:

-Is there a pre-existing autoim

mune dysfunction?

-Is there a history of prior orthopedic injury, D

JD, O

A, R

A?

-O

ther imm

une-related adverse effects-

Three subtypes of inflamm

atory arthritis associated with

checkpoint inhibitors:1.P

olyarthritis similar to rheum

atoid arthritis2.True reactive arthritis w

ith conjunctivitis, urethritis, andol igoarthritis

3.Subtype sim

ilar to seronegative spondyloarthritisw

ithinflam

matory back pain and predom

inantly larger jointinvolvem

ent.

Managem

ent

Overall Strategy:

-Assess for other etiologies,such as lytic

or osseous metastasis

-Early



OL; sym

ptomcontrol through the treatm

ent of inflamm

ation and pain is often achieved w

ith NS

AIDs, corticosteroids, and otheradjunct therapies

Grade 1 (M

ild) -

Anticipate im


-E

ncourage physical activityo

30 minutes

of low-to-m

oderate–intensity

physical activity 5 days perw

eek can improve physical

conditioning, sleep, and decreasespain perception

oFor physically inactive patients,advise supervised exercise,resistance training

oO

ther:yoga, tai chi,Qigong, Pilates,

aquaticexercise, focused dance

program-

Anticipate use of analgesiao

Low-dose N

SA

IDs

Topical:diclofenac (gel orpatch).B

est for localized,lim

ited,superficial jointinflam

mation or foruse in

patients who

cannot tolerate oralN

SA

IDs

O

ral:ibuprofen, naproxen,celecoxib

Anticipatory guidance on

proper administration

-A

ssess patientandfam




If symptom

s do notimprove in 4–6

weeks, escalate to nextlevel of therapy

Grade 2 (M

oderate)-

Ipilimum

ab to be withheld forany G

rade 2 event (until G

rade 0/1) and discontinued forevents persisting ≥6 w

eeks orinability toreduce steroid dose to 7.5 m

g prednisone orequivalent per day

-D

ose of pembrolizum


held as to not make sym

ptoms w

orse-

Pem


ab to be discontinued for G

rade 2 events persisting ≥12 w

eeks-

Continue to encourage physical activity

-A

nticipate use of analgesiao

NS

AID

s

Oral:ibuprofen, naproxen, celecoxib


administration

-A

nticipate referralto rheumatology for

collaborative managem

ent and consideration of adjuncttreatm

ent-

Anticipate pre-visit assessm

ent: CB

C, E

SR

, C

RP

, BU

N/C

R&

aminotransferases, A

NA

, RF

oIntraarticularsteroids to be used forsignificant sym

ptomatic joint(s)

oLow

-dose corticosteroids (0.5 –1

mg/kg/day) to be used


administration

D

urationof corticosteroid therapy

isusually lim

ited,lasting forabout 4–6w

eeks, with possible resolution of

symptom

sw

ithin weeks to m

onths oftreatm

ent-

Assess

patient &fam

ily understanding oftoxicity, rationale for treatm

ent hold (ifapplicable)o


If symptom

s do notimprove in 4–6 w

eeks,escalate to

nextlevel of therapy


-P

embrolizum

ab or nivolumab to be w

ithheld for first-occurrence G

rade 3/4 eventanddiscontinued if:

oG

rade 3/4 event recurso

Persists ≥12 w

eeks-

Ipilimum

ab to be discontinued for any Grade 3/4 event.

-H

igh-dose steroidsto be used (1-1.5 m

g/kg) daily; [rapid effect w

ithin days]o

Anticipatory guidance on proper adm

inistration o

Onset of action is

rapid, typically within days

-A

nticipate referralto rheumatology forcollaborative

managem

ent and consideration ofadjunct treatment

oN

on-biologicagents (m

ore likely to be recomm

ended)

Conventional synthetic

DM

AR

Ds

(csDM

AR

Ds),

which have a delayed effectand take w

eeks to w

ork:

Methotrexate

S

ulfasalazine*

Hydroxychloroquine

Leflunom

ideo

Biologic agents

(less likelyto be recom

mended)

B

iologic DM

AR

Ds (bD

MA

RD

s)

TNF inhibitors

Infliximab

E

tanercept

Adalim

umab

G

olimum

ab

Certolizum

ab pegol

Anti B

-cellagents (CD

-20 blocking)

Rituxim

ab o

Agents N

OT advised

Interleukin (IL)-6 receptor blocking agent(tocilizum

ab) and JAK

inhibitors (tofacitinib) due to risk of colonic

perforation

T cell co-stimulation inhibitor (abatacept) as it

directly opposes the mechanism

ofcheckpointblockade agents

oA

ssesspatient &

family understanding of toxicity and

rationale fortreatmentdiscontinuation

oIdentify barriers to adherence,specifically com

pliance w

ith medication,physical activity

*Sulfasalazine is associated w

ith rash; do not use in patientsw

ith history of orcurrent treatment-related derm

atitis

Grade 1 (M

ild)M

ild painG

rade 2 (Moderate)

Moderate pain; lim

iting instrum

ental AD

L

Grade 3 (Severe)

Severe pain; lim

iting self-care AD

LG

rade 4 (Potentially Life-Threatening)G

rade 5 (Death)

Grade 1 (M

ild)M

ild pain with inflam

mation,

erythema, or joint sw

elling

Grade 2 (M

oderate)M

oderate pain associated with

signs of inflamm

ation, erythema,

or joint swelling; lim

iting instrum

ental AD

L

Grade 3 (Severe)

Severe pain associated w

ith signs of inflam

mation, erythem

a, or joint sw

elling; irreversible joint damage;

disabling; limiting self-care A

DL


Grade 5 (D

eath)

Prevention-

No know

n interventions

Nursing Im

plementation:

-Identify high-risk individuals and

those with underlying autoim

mune dysfunction

-E

ducate patientsthatarthralgias and arthritis

are the mostcom

monly reported rheum

atic and musculoskeletalirA

Es w

ith checkpoint inhibitors-

Arthritis-like sym

ptoms can range from

mild (m

anaged wellw

ith NS

AID

s and low dose corticosteroids)to severe and erosive (requiring m

ultiple imm

unosuppressant medications)

-A

nticipate that the steroid requirements to m

anage arthralgias can be much higher (i.e.,up to 1.5 m

g/kg/day) thantypically required to m

anage "classic"inflamm

atory arthritis-

Educate patients

that symptom

s can persistbeyond treatment com

pletion or discontinuation

RED FLAGS:

-Risk of fall due to m

obilityissue

AD

Ls = activities ofdailyliving; A

NA

= antinuclear antibody;BU

N = blood urea nitrogen; C

BC

= complete blood count; C

R = creatinine; C

RP

= C-reactive protein; D

JD = degenerative joint disease;

DM

AR

D= disease-m

odifying antirheumatic

drug; ES

R =

erythrocyte sedimentation rate; N

SA

ID= nonsteroidal anti-inflam

matory drug; O

A = osteoarthritis; Q

OL = quality of life;R

A =

rheumatoid

arthritis; RF = rheum

atoid factor;TNF = tum

or necrosis factor

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Arthralgias and A


Care Step Pathw

ay-Arthralgias and

Arthritis

Nursing Assessm

entLook:-


fortable?-


ell?-


Obvious sw

ollen,ordeformed joint(s)?

-Is the patienthaving trouble getting up and dow

n stairs?

Grading Toxicity

Arthralgia

Definition: A

disorder characterized bya sensation ofm

arked discomfort in a joint

Arthritis

Definition: A

disorder characterized byinflam


Listen:-

Have sym

ptoms w

orsened? -

Are sym

ptoms lim

iting AD

Ls?-

Are sym


fall? Othersafety issues?

-A

ssociated symptom

s?o

Fatigue (new or w

orsening)

Recognize:


mune dysfunction?

-Is there a history ofpriororthopedic injury, D

JD, O

A, R

A?

-O

ther imm


Three subtypes ofinflamm


checkpointinhibitors:1.P

olyarthritissim

ilar to rheumatoid arthritis

2.True reactive arthritis with conjunctivitis, urethritis,and

oligoarthritis3.S

ubtype similar to seronegative spondyloarthritis

with

inflamm

atory back pain and predominantly larger joint

involvement.

Managem

ent

Overall Strategy:

-Assess for other etiologies,such as lytic or osseous m

etastasis-

Early intervention to maintain or im


OL; sym


ent of inflamm

ation and pain is often achievedw

ith NS

AIDs, corticosteroids, and other adjunct therapies

Grade 1 (M

ild) -

Anticipate im


-E


30 minutes of low

-to-moderate–

intensity physical activity 5 days perw



oFor physically inactive patients,advise supervised exercise,resistance traini ng

oO

ther: yoga, tai chi, Qigong, Pilates,

aquatic exercise, focused danceprogram

-A


Low-dose N

SA

IDs




mation or for use i n

patients who


SA

IDs

O


Anticipatory guidance o n


-A

ssess patient andfam

ily understandingof recom



If symptom

s do not improve in 4–6

weeks, escalate to next level of therapy

Grade 2 (M

oderate)-

Ipilimum


rade 2event (until G


eeks or inability toreduce steroid dose to 7.5 m


-D

ose of pembrolizum

ab or nivolumab t o be


ptoms w

orse-

Pem


ab to bediscontinued for G

rade 2 events persisting ≥1 2w

eeks-


-A


NS

AID

s



administration

-A

nticipate referral to rheumatology for


ent and considerati onof adjunct treatm

ent-


ent: CB

C, E

SR

,C

RP

, BU

N/C

R&


NA

, RF

oIntraarticular steroids to be used forsignificant sym

ptomatic joint(s)

oLow




administration

D

uration of corticosteroid therapy isusually lim

ited, lasting for about 4–6w


symptom

s within w

eeks to months of

treatment

-A

ssess patient & fam




If symptom

s do not improve in 4–6 w

eeks, escalate to next level of therapy


-P

embrolizum



rade 3/4 event anddiscontinued if:

oG


Persists ≥12 w

eeks-

Ipilimum


-H

igh-dose steroids to be used (1-1.5 mg/kg) daily; [rapi d

effect within days]

oA

nticipatory guidance on proper administration

oO

nset of action is rapid, typically within days

-A

nticipate referral to rheumatology for collaborative

managem

ent and consideration of adjunct treatment

oN

on-biologic agents (more likely to be recom

mended)

C

onventional synthetic DM

AR

Ds

(csDM

AR

Ds),

which have a delayed effect and take w

eeks tow

o rk:

Methotrexate

S

ulfasalazine*

Hydroxychloroquine

Lef lunom

ideo

Biologic agents (less likely to be recom

mended)

B

iologic DM

AR

Ds (bD

MA

RD

s)

TNF inhibitors

Infliximab

E

tanercept

Adalim

umab

G

olimum

a b

Certolizum

ab pegol

Anti B

-cell agents (CD

-20 blocking)

Rituxim

abo

Agents N

OT advis ed


ab) and JAK

inhibitors (tofacitinib) d ueto risk of colonic perforation

T cell co-stim

ulation inhibitor (abatacept) as itdirectly opposes the m

echanism of checkpoint

blockade agentso

Assess patient &


r ationale for treatment discontinuation

oIdentify barriers to adherence, specifically com

pliancew

ith medication, physical activity



ith history of or current treatment-related derm

atitis

Grade 1 (M

ild)M

ild painG

rade 2 (Moderate)

Moderate pain; lim

itinginstrum

ental AD

L

Grade 3 (Severe)

Severe pain; lim

iting self-care AD

LG


rade 5 (Death)

Grade 1 (M

ild)M


mation,

erythema, or jointsw

elling

Grade 2 (M

oderate)M


signs of inflamm

ation, erythema,

or jointswelling; lim

iting instrum

ental AD

L

Grade 3 (Severe)


ith signsof inflam

mation, erythem

a,or jointsw

elling; irreversible jointdamage;


DL


Grade 5 (D

eath)

Prevention -

No know

n interventions

Nursing Im

plementation:

-Identify high-risk individuals and

those with underlying autoim

mune dysfunction

-E

ducate patientsthatarthralgias and arthritis

are the mostcom

monly reported rheum

atic and musculoskeletalirA

Es w

ith checkpoint inhibitors-

Arthritis-like sym

ptoms can range from

mild (m

anaged wellw

ith NS

AID

s and low dose corticosteroids)to severe and erosive (requiring m

ultiple imm

unosuppressant medications)

-A

nticipate that the steroid requirements to m

anage arthralgias can be much higher (i.e.,up to 1.5 m

g/kg/day) thantypically required to m

anage "classic"inflamm

atory arthritis-

Educate patients

that symptom

s can persistbeyond treatment com


RED FLAGS:


obilityissue

AD

Ls = activities ofdailyliving; A

NA

= antinuclear antibody;BU

N = blood urea nitrogen; C

BC

= complete blood count; C

R = creatinine; C

RP

= C-reactive protein; D

JD = degenerative joint disease;

DM

AR

D= disease-m

odifying antirheumatic

drug; ES

R =

erythrocyte sedimentation rate; N

SA

ID= nonsteroidal anti-inflam

matory drug; O

A = osteoarthritis; Q

OL = quality of life;R

A =

rheumatoid



or necrosis factor

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Arthralgias and A


Care Step Pathw

ay-Arthralgias and

Arthritis

Nursing Assessm

entLook:-


fortable?-


ell?-


Obvious sw

ollen,ordeformed joint(s)?

-Is the patienthaving trouble getting up and dow

n stairs?

Grading Toxicity

Arthralgia

Definition: A

disorder characterized bya sensation ofm

arked discomfort in a joint

Arthritis

Definition: A

disorder characterized byinflam


Listen:-

Have sym

ptoms w

orsened? -

Are sym

ptoms lim

iting AD

Ls?-

Are sym


fall? Othersafety issues?

-A

ssociated symptom

s?o

Fatigue (new or w

orsening)

Recognize:


mune dysfunction?

-Is there a history ofpriororthopedic injury, D

JD, O

A, R

A?

-O

ther imm


Three subtypes ofinflamm


checkpointinhibitors:1.P

olyarthritissim

ilar to rheumatoid arthritis

2.True reactive arthritis with conjunctivitis, urethritis,and

oligoarthritis3.S

ubtype similar to seronegative spondyloarthritis

with

inflamm

atory back pain and predominantly larger joint

involvement.

Managem

ent

Overall Strategy:

-Assess for other etiologies,such as lytic

or osseous metastasis

-Early



OL; sym


ent of inflamm

ation and pain is often achieved w

ith NS

AIDs, corticosteroids, and otheradjunct therapies

Grade 1 (M

ild) -

Anticipate im


-E


30 minutes

of low-to-m

oderate–intensity

physical activity 5 days perw



oFor physically inactive patients,advise supervised exercise,resistance training

oO

ther:yoga, tai chi,Qigong, Pilates,

aquaticexercise, focused dance

program-

Anticipate use of analgesiao

Low-dose N

SA

IDs




mation or foruse in

patients who


SA

IDs

O


Anticipatory guidance on


-A

ssess patientandfam




If symptom

s do notimprove in 4–6

weeks, escalate to nextlevel of therapy

Grade 2 (M

oderate)-

Ipilimum

ab to be withheld forany G

rade 2 event (until G


eeks orinability toreduce steroid dose to 7.5 m


-D

ose of pembrolizum



ptoms w

orse-

Pem


ab to be discontinued for G


eeks-


-A


NS

AID

s



administration

-A

nticipate referralto rheumatology for


ent and consideration of adjuncttreatm

ent-


ent: CB

C, E

SR

, C

RP

, BU

N/C

R&


NA

, RF

oIntraarticularsteroids to be used forsignificant sym

ptomatic joint(s)

oLow




administration

D

urationof corticosteroid therapy

isusually lim

ited,lasting forabout 4–6w


symptom

sw

ithin weeks to m

onths oftreatm

ent-

Assess

patient &fam




If symptom

s do notimprove in 4–6 w

eeks,escalate to

nextlevel of therapy


-P

embrolizum



rade 3/4 eventanddiscontinued if:

oG


Persists ≥12 w

eeks-

Ipilimum


-H

igh-dose steroidsto be used (1-1.5 m

g/kg) daily; [rapid effect w

ithin days]o


inistration o

Onset of action is

rapid, typically within days

-A

nticipate referralto rheumatology forcollaborative

managem

ent and consideration ofadjunct treatment

oN

on-biologicagents (m

ore likely to be recomm

ended)

Conventional synthetic

DM

AR

Ds

(csDM

AR

Ds),

which have a delayed effectand take w

eeks to w

ork:

Methotrexate

S

ulfasalazine*

Hydroxychloroquine

Leflunom

ideo

Biologic agents

(less likelyto be recom

mended)

B

iologic DM

AR

Ds (bD

MA

RD

s)

TNF inhibitors

Infliximab

E

tanercept

Adalim

umab

G

olimum

ab

Certolizum

ab pegol

Anti B

-cellagents (CD

-20 blocking)

Rituxim

ab o

Agents N

OT advised


ab) and JAK

inhibitors (tofacitinib) due to risk of colonic

perforation

T cell co-stimulation inhibitor (abatacept) as it

directly opposes the mechanism

ofcheckpointblockade agents

oA

ssesspatient &


rationale fortreatmentdiscontinuation

oIdentify barriers to adherence,specifically com

pliance w

ith medication,physical activity



ith history of orcurrent treatment-related derm

atitis

Grade 1 (M

ild)M

ild painG

rade 2 (Moderate)

Moderate pain; lim

itinginstrum

ental AD

L

Grade 3 (Severe)

Severe pain; lim

iting self-care AD

LG


rade 5 (Death)

Grade 1 (M

ild)M


mation,

erythema, or jointsw

elling

Grade 2 (M

oderate)M


signs of inflamm

ation, erythema,

or jointswelling; lim

iting instrum

ental AD

L

Grade 3 (Severe)


ith signsof inflam

mation, erythem

a,or jointsw

elling; irreversible jointdamage;


DL


Grade 5 (D

eath)

Prevention-

No know

n interventions

Nursing Im

plementation:

-Identify high-risk individuals and those w

ith underlying autoimm

une dysfunction-

Educate patients that arthralgias and arthritis are the m

ost comm

only reported rheumatic and m

usculoskeletal irAE

s with checkpoint inhibitors

-A

rthritis-like symptom

s can range from m

ild (managed w

ell with N

SA

IDs and low

dose corticosteroids)to severe and erosive (requiring multiple im

munosuppressant m

edications)-

Anticipate that the steroid requirem

ents to manage arthralgias can be m

uch higher (i.e., up to 1.5 mg/kg/day) than

typically required to manage "classic"inflam

matory arthritis

-E

ducate patients that symptom

s can persist beyond treatment com


RED FLAGS:


obility issue

AD

Ls = activities of daily living; AN

A= antinuclear antibody; B

UN

= blood urea nitrogen; CB

C = com

plete blood count; CR

= creatinine; CR

P = C

-reactive protein; DJD

= degenerative joint disease; D

MA

RD

= disease-modifying antirheum

atic drug; ES

R = erythrocyte sedim

entation rate; NS

AID

= nonsteroidal anti-inflamm

atory drug; OA

= osteoarthritis; QO

L = quality of life;RA

= rheumatoid



or necrosis factor

Copyright ©

2017 Melanom


Care Step Pathw

ay –N

europathy (motor or sensory nerve im

pairment or dam

age)

Nursing Assessm

ent

Look:-


eak?-


fortable?-

Altered am

bulation or general movem

ent?-

If muscular w

eakness is present, any respiratory difficulties apparent?

Grading of N

europathy:

Listen:-

Does the patient report w

eakness (unilateral or bilateral)?

-D

oes the patient report new or w

orsened pain, num

bness, or tingling?-

Does the patient report difficulty w

alking or holding item

s?

Recognize:

-M

otor deficits-

Sensory deficits

-M

ental status changes-

Paresthesias

-Laboratory values

-D

oes the patient have diabetes mellitus?

-A

re there neurologic signs and symptom

s?-

Results of prior im

aging o

Metastases to spinal cord

oO

ther metastases that m

ay cause symptom

s

Managem

entO

verall Strategy:-

Rule out infectious, non-infectious, disease-related etiologies

-H

igh-dose steroids (1–2 mg/kg/day prednisone or equivalent) to be used

-Ipilim

umab to be w

ithheld for Grade 2 event, nivolum

ab for firstoccurrence of Grade 3 event, and pem

brolizumab based on disease severity; ipilim

umab to be discontinued for G


eeks or inability to reduce steroid dose to ≤7.5 mg prednisone or equivalent per day; pem


ab to be discontinued for Grade 3/4 events that recur,

persist ≥12 weeks, or inability to reduce steroid dose to ≤10 m


Neurology consulto

Consideration of electrom

yelogram and nerve conduction tests

oIm

mune globulin infusions

oP

lasmapheresis

-Taper steroids slow

ly over at least 4 weeks once sym

ptoms im

prove-

If needed, obtain physical therapy or occupational therapy consult (for both functional assessment and evaluate safety of patient at hom

e)-

Supportive m

edications for symptom

atic managem

ent

Grade 1 (M

ild)P

eripheral Motor:

-A

symptom

atic; clinical or diagnostic observations only

-N

o intervention indicated

Peripheral Sensory:

Asym

ptomatic;loss of deep tendon

reflexes or paresthesia

Grade 2 (M

oderate)P

eripheral Motor:

Moderate sym

ptoms; lim

iting A

DLs

Peripheral Sensory:

Moderate sym

ptoms; lim

iting A

DLs

Grade 3 (Severe)

Peripheral M

otor:S

evere symptom

s; limiting self-

care AD

Ls; requires assistive devices

Peripheral Sensory:

Severe sym

ptoms; lim

iting self-care A

DLs


Peripheral M

otor:Life-threatening;urgent intervention indicated

Peripheral Sensory:

Life-threatening;urgent intervention indicated

Grade 5 (D

eath)

Nursing Im

plementation:

-C


ent;grade & docum

ent neuropathy and etiology (diabetic, medication, vascular, chem

otherapy)-

Early identification and evaluation of patient sym

ptoms

-E


ork and office visit if neuropathy symptom

ssuspected

RED FLAGS:

-G

uillain–Barré syndrome

-M

yasthenia gravis

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-term

high-dosesteroids:

-C







-C


Avoid


orotherhepatoxins

AD

Ls = activities of daily living

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Neuropathy Page 1 of 2

Care Step Pathw

ay –N

europathy (motor or sensory nerve im

pairment or dam

age)

Nursing Assessm

ent

Look:-


eak?-


fortable?-

Altered am

bulation or general movem

ent?-

If muscular w

eakness is present, any respiratory difficulties apparent?

Grading of N

europathy:

Listen:-

Does the patient report w

eakness (unilateral or bilateral)?

-D

oes the patient report new or w

orsened pain, num

bness, or tingling?-

Does the patient report difficulty w

alking or holding item

s?

Recognize:

-M

otor deficits-

Sensory deficits

-M

ental status changes-

Paresthesias

-Laboratory values

-D

oes the patient have diabetes mellitus?

-A

re there neurologic signs and symptom

s?-

Results of prior im

aging o

Metastases to spinal cord

oO

ther metastases that m

ay cause symptom

s

Managem

entO

verall Strategy:-

Rule out infectious, non-infectious, disease-related etiologies

-H

igh-dose steroids (1–2 mg/kg/day prednisone or equivalent) to be used

-Ipilim

umab to be w

ithheld for Grade 2 event, nivolum

ab for firstoccurrence of Grade 3 event, and pem

brolizumab based on disease severity; ipilim

umab to be discontinued for G


eeks or inability to reduce steroid dose to ≤7.5 mg prednisone or equivalent per day; pem


ab to be discontinued for Grade 3/4 events that recur,

persist ≥12 weeks, or inability to reduce steroid dose to ≤10 m


Neurology consulto

Consideration of electrom

yelogram and nerve conduction tests

oIm

mune globulin infusions

oP

lasmapheresis

-Taper steroids slow

ly over at least 4 weeks once sym

ptoms im

prove-

If needed, obtain physical therapy or occupational therapy consult (for both functional assessment and evaluate safety of patient at hom

e)-

Supportive m

edications for symptom

atic managem

ent

Grade 1 (M

ild)P

eripheral Motor:

-A

symptom

atic; clinical or diagnostic observations only

-N

o intervention indicated

Peripheral Sensory:

Asym

ptomatic;loss of deep tendon

reflexes or paresthesia

Grade 2 (M

oderate)P

eripheral Motor:

Moderate sym

ptoms; lim

iting A

DLs

Peripheral Sensory:

Moderate sym

ptoms; lim

iting A

DLs

Grade 3 (Severe)

Peripheral M

otor:S

evere symptom

s; limiting self-

care AD

Ls; requires assistive devices

Peripheral Sensory:

Severe sym

ptoms; lim

iting self-care A

DLs


Peripheral M

otor:Life-threatening;urgent intervention indicated

Peripheral Sensory:

Life-threatening;urgent intervention indicated

Grade 5 (D

eath)

Nursing Im

plementation:

-C


ent;grade & docum

ent neuropathy and etiology (diabetic, medication, vascular, chem

otherapy)-

Early identification and evaluation of patient sym

ptoms

-E


ork and office visit if neuropathy symptom

ssuspected

RED FLAGS:

-G

uillain–Barré syndrome

-M

yasthenia gravis

*Steroid


guidebutnotan

absolute-


currentsymptom

profile-

Close

follow-up

inperson

orbyphone,based

onindividualneed

&sym

ptomatology

-A

nti-acidtherapy

dailyas


while

onsteroids

-R

eviewsteroid

medication

sideeffects:m

oodchanges




-B

ealertto

recurringsym

ptoms

assteroids

taperdown

& reportthem

(tapermay

needto

beadjusted)

Long-term

high-dosesteroids:

-C







-C


Avoid


orotherhepatoxins

AD

Ls = activities of daily living

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Neuropathy Page 2 of 2

© 2017 The M

elanoma N


ww

w.them

elanomanurse.org

Nephritis Page 1 of 3

Care Step Pathw

ay –N

ephritis(inflam

mation of the kidneys)

Nursing Assessm

ent

Look:-


fortable?-


Grading Toxicity

Acute K

idney Injury, Elevated Creatinine

Definition: A disorder characterized by the acute loss of renal function and

is traditionally classified as pre-renal, renal, and post-renal.

Listen:-

Has there been change in urination? o

Urine color?

oFrequency?

-H

ow m

uch fluid is the patient taking in?-

Are associated sym

ptoms present?

oN

ausea?o

Headache?

oM

alaise? o

Lungedem

a?-

Are there

symptom

s concerning for:o

Urinary tract infection?

oP

yelonephritis? o

Worsening C

HF?

-A

re symptom

s limiting A

DLs?

-C

urrent or recent use of nephrotoxic medications

(prescribed and OTC

) other agents?o

NS

AID

so

Antibiotics

oC

ontrast media or other nephrotoxic agents

(contrastdye, aminoglycosides, P

PI)?

Recognize:

-Laboratory abnorm

alities (elevated creatinine, electrolyte abnorm

alities)-

Urinalysis abnorm

alities (casts)-

Abdom

inal or pelvic disease that could be causing sym

ptoms

-P

riorhistory of renal comprom

ise? -

Other im

mune-related adverse effects?

-P

resence of current or prior imm

une-mediated

toxicities,including rhabdomyolysis

-Is patient volum

e depleted?

Managem

ent

Overall Strategy

-Assess for other etiologies,such as infection

-Elim

inate potentially nephrotoxic medications

-Ensure adequate hydration daily

-Evaluate for progressive kidney/adrenal/pelvic m

etastases that may be contributing to kidney dysfunction


aintain orimprove physical function and im

pact on QO

L

Mild elevation in creatinine (G

rade 1)-

Anticipate im


-P

erform detailed review

of concomitant

medications (prescribed and O

TC),

herbals,vitamins,anticipating possible

discontinuation of nephrotoxic agents-

Avoid/m

inimize addition of nephrotoxic

agents,such as contrast media for

radiology tests -

Anticipate close m

onitoringofcreatinine

(i.e.,weekly)

-E

ducate patient/family on im

portance of adequate daily hydration

and set individualized

hydration goals-

Review

symptom

s to watch for w

ith patient and fam

ily and remem

ber to assess at subsequent visits

Moderate elevation in creatinine (G

rade 2)-

Ipilimum

abto be w

ithheldfor any G


rade 0/1) and discontinued

for events persisting ≥6 weeks or inability to

reduce steroid dose to 7.5 mg prednisone/day

-P

embrolizum


ithheld for Grade 2 events

persisting ≥12 weeks or inability to reduce steroid dose to ≤10 m

g prednisone or equivalent per day

-A

nticipate increase in frequency of creatininem

onitoring (i.e.,every 2–3 days until im

provement)

-Im

munosuppressive

medications to be initiated to treat im

mune-

mediated nephritis o

System

ic corticosteroids (e.g.,prednisone)0.5–1 mg/kg/day

until symptom

improve to baseline follow

ed by slowtaper

over at least 1m

ontho

Anticipate increased

in corticosteroid dosing (i.e.,treat as if G

rade 3 nephritis) if creatinine does not improve w

ithin 48–72hours

oA

nticipate use of additional supportive care medications

-U

pon symptom

sresolution to patient’s baseline, orG

rade 1, begin

to tapercorticosteroid dose slowly over 1 m

onth-


inistration -

Anticipate the use of IV

fluid to ensure adequate hydration-

Anticipate that nephrology consultation m

ay be initiated by provider

-A

ssess patient & fam

ily understanding of recomm

endations and rationale


Moderate (G

rade 3)and Severe (Grade 4)

-P

embrolizum



rade 3/4 event anddiscontinued

if:o

Grade 3/4 event recurs

oP

ersists ≥12 weeks

oR

equires >10 mg prednisone or equivalent per day for m

ore than 12 w

eeks. -

Ipilimum

ab to be discontinued for any Grade 3/4 event

-Im

munosuppressive m

edications to be initiated to treat imm

une-m

ediated nephritiso

Corticosteroids (e.g., prednisone 1–2 m

g/kg/day, in divided doses)until sym

ptoms

improve to baseline and then slow

taper over at least 1

month

oIf sym

ptoms do not im

prove within 48–72 hours, additional

imm

unosuppressivem

edications will be considered

-A

nticipate nephrologyconsultation

will be initiated by provider

-A

nticipate that renal biopsy will be considered

-H

emodialysis m

ay be considered-

Anticipate possible hospital adm

ission for Grade 4 elevations in

creatinine or in patients with m

ultiple comorbidities

Grade 1 (M

ild)C

reatinine level >0.3 mg/dL;

creatinine 1.5–2×U

LN

Grade 2 (M

oderate)C

reatinine 2–3×U

LNG

rade 3 (Severe)C

reatinine >3×U

LN or > 4.0

mg/dL; hospitalization indicated


Life-threatening consequences; dialysis indicated

Grade 5

(Death)

Nursing Im

plementation:

-Identify

individualsw

ith pre-existing renal dysfunction prior to initiating imm

unotherapy. Ensure

baseline creatininehas been

obtained-

Check kidney function prior to each dose of im

munotherapy

-M

onitor creatinine more frequently if levels appear to be rising,and for G

rade 1 toxicity-

Educate patients that new urinary sym

ptoms


ediately-

Anticipate the steroid requirements to m

anage imm

une-mediated nephritis are high

(up to 1 –2 mg/kg/d)and patients

will be on corticosteroid therapy for at least 1

month



unotherapy in patients who develop severe nephritis

RED FLAGS:


-Risk of m

ortality if unrecognized or treatment is delayed

-Risk of im

mune-m

ediated nephritis is greater in patients receiving combination im

munotherapy regim

ens and PD-1 inhibitors -

In addition to acute interstitial nephritis seen from PD-1 inhibitors, there are case reports of lupus-like nephritis and granulom

atous acute interstitial nephritis

AD

Ls = activities of daily living; CH

F = congestiveheart failure; LE

= lung edema; N

SA

IDs


atory drugs; OTC

= over the counter; PP

I = proton pump inhibitor;

QO

L= quality of life; U

LN = upper lim

it of normal.

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org


Care Step Pathw

ay –N

ephritis(inflam


Nursing Assessm

ent

Look:-


fortable?-


Grading Toxicity

Acute K




Listen:-


Urine color?

oFrequency?

-H

ow m


Are associated sym

ptoms present?

oN

ausea?o

Headache?

oM

alaise? o

Lungedem

a?-

Are there

symptom

s concerning for:o


oP

yelonephritis? o

Worsening C

HF?

-A

re symptom

s limiting A

DLs?

-C


(prescribed and OTC

) other agents?o

NS

AID

so

Antibiotics

oC



PI)?

Recognize:

-Laboratory abnorm


alities)-

Urinalysis abnorm

alities (casts)-

Abdom


ptoms

-P


ise? -

Other im


-P


une-mediated


-Is patient volum

e depleted?

Managem

ent

Overall Strategy


-Elim







pact on QO

L


rade 1)-

Anticipate im


-P


of concomitant


TC),



Avoid/m



radiology tests -

Anticipate close m


(i.e.,weekly)

-E




hydration goals-

Review

symptom

s to watch for w

ith patient and fam

ily and remem



rade 2)-

Ipilimum

abto be w

ithheldfor any G





-P

embrolizum





-A



provement)

-Im

munosuppressive


mune-


System


until symptom


ed by slowtaper

over at least 1m

ontho




ithin 48–72hours

oA


-U

pon symptom


rade 1, begin


onth-


inistration -





-A

ssess patient & fam




Moderate (G


-P

embrolizum




if:o


oP

ersists ≥12 weeks

oR


ore than 12 w

eeks. -

Ipilimum


-Im

munosuppressive m


une-m

ediated nephritiso



ptoms



month

oIf sym

ptoms do not im


imm

unosuppressivem


-A



-A


-H

emodialysis m

ay be considered-





Grade 1 (M

ild)C



LN

Grade 2 (M

oderate)C

reatinine 2–3×U

LNG

rade 3 (Severe)C

reatinine >3×U

LN or > 4.0




Grade 5

(Death)

Nursing Im

plementation:

-Identify

individualsw


unotherapy. Ensure


obtained-


munotherapy

-M


rade 1 toxicity-


ptoms


ediately-


anage imm




month




RED FLAGS:


-Risk of m


-Risk of im

mune-m


munotherapy regim




AD



= lung edema; N

SA

IDs


atory drugs; OTC



QO


LN = upper lim

it of normal.

Copyright ©

2017 Melanom


© 2017 The M

elanoma N


ww

w.them

elanomanurse.org


Care Step Pathw

ay –N

ephritis(inflam


Nursing Assessm

ent

Look:-


fortable?-


Grading Toxicity

Acute K




Listen:-


Urine color?

oFrequency?

-H

ow m


Are associated sym

ptoms present?

oN

ausea?o

Headache?

oM

alaise? o

Lungedem

a?-

Are there

symptom

s concerning for:o


oP

yelonephritis? o

Worsening C

HF?

-A

re symptom

s limiting A

DLs?

-C


(prescribed and OTC

) other agents?o

NS

AID

so

Antibiotics

oC



PI)?

Recognize:

-Laboratory abnorm


alities)-

Urinalysis abnorm

alities (casts)-

Abdom


ptoms

-P


ise? -

Other im


-P


une-mediated


-Is patient volum

e depleted?

Managem

ent

Overall Strategy


-Elim







pact on QO

L


rade 1)-

Anticipate im


-P


of concomitant


TC),



Avoid/m



radiology tests -

Anticipate close m


(i.e.,weekly)

-E




hydration goals-

Review

symptom

s to watch for w

ith patient and fam

ily and remem



rade 2)-

Ipilimum

abto be w

ithheldfor any G





-P

embrolizum





-A



provement)

-Im

munosuppressive


mune-


System


until symptom


ed by slowtaper

over at least 1m

ontho




ithin 48–72hours

oA


-U

pon symptom


rade 1, begin


onth-


inistration -





-A

ssess patient & fam




Moderate (G


-P

embrolizum




if:o


oP

ersists ≥12 weeks

oR


ore than 12 w

eeks. -

Ipilimum


-Im

munosuppressive m


une-m

ediated nephritiso



ptoms



month

oIf sym

ptoms do not im


imm

unosuppressivem


-A



-A


-H

emodialysis m

ay be considered-





Grade 1 (M

ild)C



LN

Grade 2 (M

oderate)C

reatinine 2–3×U

LNG

rade 3 (Severe)C

reatinine >3×U

LN or > 4.0




Grade 5

(Death)

Nursing Im

plementation:

-Identify

individualsw


unotherapy. Ensure


obtained-


munotherapy

-M


rade 1 toxicity-


ptoms


ediately-


anage imm




month




RED FLAGS:


-Risk of m


-Risk of im

mune-m


munotherapy regim




AD



= lung edema; N

SA

IDs


atory drugs; OTC



QO


LN = upper lim

it of normal.

Copyright ©

2017 Melanom


APPENDIX 2




Adverse event Common symptoms Common management/anticipatory guidance

Acute respiratory distress syndrome

Severe shortness of breath, dyspnea, or rapid breathing, hypotension, confusion, and extreme fatigue

• Serious condition requiring hospitalization/expert care, including supplemental oxygen, often mechanical ventilation, and fluid management

Anorexia Decreased appetite

• Monitor weight; query patient about appetite/eating habits; advise dietary modification if necessary (should improve with time)

• Anticipate standard dose holds/discontinuations*• Consider referral to nutrition services for counseling on best food

choices to avoid excessive weight loss

Cardiotoxicity: cardiomyopathy, myocarditis, heart failure

Dyspnea, edema, fatigue, chest pain, arrhythmias, abdominal pain or ascites

• Monitor weight, changes in breathing, extremity edema, chest/back/arm/jaw pain, pressure

• ECG, Echo, stress test cardiology referral, 2 mg/kg prednisone, discontinue therapy

Embryo-fetal toxicity ––

• Advise of risk to fetus and recommend use of effective contraception during treatment and for 3 months after ipilimumab and for 5 months after nivolumab is discontinued

• Advise patient to tell HCP immediately if they or their partner suspect they are pregnant while taking therapy

Encephalitis

Headache, fever, tiredness, confusion, memory problems, sleepiness, hallucinations, seizures, stiff neck

• New-onset (Grade 2–3) moderate to severe symptoms: rule out infectious or other causes; consult neurologist, obtain brain MRI, and lumbar puncture

• For ipilimumab: Anticipate standard ipilimumab dose holds/discontinuations;* administer corticosteroids at dose of 1–2 mg/kg/d prednisone equivalents (or 2–4 mg/kg if necessary)

• For nivolumab: Withhold nivolumab for new-onset moderate to severe neurologic symptoms; evaluate as described above; if other etiologies are ruled out, administer corticosteroids and permanently discontinue nivolumab for immune-mediated encephalitis

Fatigue Feeling tired; lack of energy

• Query patients regarding energy level; evaluate possible contributory factors, including infection, disease progression, and hematological and metabolic abnormalities; standard supportive care

• Anticipate standard dose holds/discontinuations*• Fatigue that interferes with ADLs is concerning and should be

evaluated for underlying causes

Management of other AEs associated with ipilimumab therapy



Adverse event Common symptoms Common management/anticipatory guidance

Headache Head pain

• Need to rule out brain metastases, encephalitis, or hypophysitis; otherwise, standard supportive care (should improve with time)

• Headache occurring in conjunction with fatigue could be indicative of hypophysitis

• Anticipate standard dose holds/discontinuations*

Infusion reaction

Chills/shaking, back pain, itching, flushing, difficulty breathing, hypotension, fever

• Nivolumab and/or ipilimumab: For mild/moderate (Grade 1–2) reactions: interrupt or slow rate of infusion; monitor to recovery.

• For severe/life-threatening (Grade 3–4) reactions: Discontinue nivolumab and/or ipilimumab; manage anaphylaxis via institutional protocol; monitor. Premedication with an antipyretic and antihistamine may be considered for future doses

Insomnia Difficulty falling or staying asleep

• Counsel patients on good sleep habits; prescription medications can be used if needed (should improve over time)

• May be related to steroid use• Anticipate standard dose holds/discontinuations*

Nausea/vomiting Vomiting, queasiness, RUQ or LUQ pain

• May indicate hepatotoxicity; check LFTs/lipase/amylase; standard supportive care

• Anticipate dose holds/discontinuations*

Ocular: conjunctivitis, blepharitis, episcleritis, iritis, ocular myositis, scleritis, uveitis (associated with ipilimumab)

Blurry vision, double vision, or other vision problems, eye pain or redness

• Encourage patient to report any eye symptoms immediately• Obtain ophthalmology referral• Anticipate standard dose ipilimumab holds/discontinuations*

Pyrexia Elevated body temperature

• Standard supportive care related to cytokine release• Consider infectious workup for prolonged elevated temperature• Anticipate standard dose holds/discontinuations*

Rhabdomyolysis

Pain, muscle weakness, vomiting, confusion, tea-colored urine

• Anticipate does holds/discontinuations*• Intravenous fluids and corticosteroids (check creatine kinase levels)

*Withhold ipilimumab for any G2 (moderate) AE, and resume treatment when AE returns to G0 or 1; permanently discontinue for any G3–4 (life-threatening) AE, persistent G2 AE lasting ≥6 weeks, or inability to reduce corticosteroid dose to 7.5 mg/d prednisone or equivalent.

Management of other AEs associated with ipilimumab therapy (Continued)

Ipilimumab Monotherapy for Melanoma: A Nursing Toolkit ...themelanomanurse.org/wp-content/uploads/2019/05/MNI-toolkit-IPI-… · melanoma and as an adjuvant treatment of resected

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