6/15/2020 1 Myelodysplastic Syndromes (MDS): Diagnosis, Treatment, and Side Effects Management Learning Objectives • Describe the various types and subtypes of MDS • Identify tests used to diagnose disease and monitor treatment of MDS • Explain the overarching goals of treatment for the types of MDS • Explain approved and emerging treatment options for MDS, including stem cell transplantation, and the role of clinical trials • Describe the roles of the pharmacist, the nurse and the social worker in treating patients with MDS 1 2
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Learning Objectives - LLSCE · 2020-06-15 · –MDS with multilineage dysplasia (MDS-MLD) –MDS with excess blasts-1(MDS-EB-1) –MDS with excess blasts-2 (MDS-EB-2) –MDS, unclassifiable
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6/15/2020
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Myelodysplastic Syndromes (MDS):Diagnosis, Treatment, and Side Effects Management
Learning Objectives
• Describe the various types and subtypes of MDS
• Identify tests used to diagnose disease and monitor treatment of MDS
• Explain the overarching goals of treatment for the types of MDS
• Explain approved and emerging treatment options for MDS, including stem cell transplantation, and the role of clinical trials
• Describe the roles of the pharmacist, the nurse and the social worker in treating patients with MDS
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Faculty
Sangmin Lee, MDAssistant Professor of Medicine
Weill Cornell Medical College
Assistant Attending Physician
New York-Presbyterian Hospital
New York, NY
Peter Campbell, PharmD, BCOPClinical Pharmacy Manager,
Hematology/OncologyColumbia University Irving Medical Center
New York, NY
Ayelet Nelson, MSW, ANP-BCAdult Care Nurse Practitioner
Weill Cornell MedicineNew York, NY
Myelodysplastic Syndrome (MDS)
Sangmin Lee, MD
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What Is MDS?
• MDS = myelodysplastic syndrome
• Group of heterogeneous clonal bone marrow disorders with dysplastic and ineffective hematopoiesis and increased risk of transformation to leukemia
• Most commonly diagnosed myeloid neoplasm in U.S.
– Incidence: 4.6/100,000
• Predominantly disease of the elderly
– ~86% patients are older than 60 at diagnosis
Diagnostic Workup for MDS
• Complete blood count with (manual differential), serum erythropoietin
level in certain cases
• Bone marrow biopsy/aspirate
o Morphology
─ Dysplasia, blasts, ring sideroblasts
o Flow cytometry
o Cytogenetics
─ Evaluate for cytogenetic abnormalities associated with MDS
o Mutation testing
─ Most often myeloid mutation panel using next-generation
– Decreased infections requiring IV antibiotics by 33%
• Most common side effects: cytopenias, injection site reaction, nausea, vomiting, fatigue, diarrhea
Fenaux, et al. Lancet Oncology 2009;10: 223-32
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Decitabine (Dacogen®) in
High-risk MDS
• Phase III randomized study of decitabine vs
supportive care:
– CR: 9% vs 0%, p<0.001
– Hematologic improvement: 13% vs 7% p<0.001
– Overall improvement (CR+PR+HI): 30% vs 7% p<0.001
– Time to AML or death: 12.1 mo vs 7.8 mo (p=0.16)
Kantarjian Cancer 2006
Azacitidine (Vidaza®) Prolongs Survival in
High-Risk MDS but Outcome Is Dismal
After Azacitidine (Vidaza®) Failure
Median overall survival 4-6 months
Prebet et al. JCO. 2011.
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Continued Azacitidine (Vidaza®) in
Stable Disease May Be Beneficial
Papageorgiou SG. Hematol Oncol. 2018.
How About Decitabine (Dacogen®)
After Azacitidine (Vidaza®)?
• Response low (ORR ~19% in one study, no CR)
• Responses short (2-5 months)
• Survival short (5.9-7.3 months)
Harel et al. Leuk Res. 2015.
Duong et al. Leuk Lymphoma. 2015.
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HMA in Lower Risk MDS
• Azacitidine (Vidaza®):
– Azacitidine (Vidaza®) 75mg/m2 SC for 5 days
– 38% Hematologic improvement, 19% CR, 65% stable
disease
• Decitabine (Dacogen®):
– Decitabine (Dacogen®) 20mg/m2 SC for 3 days
– Overall improvement rate (CR, PR, HI): 23%,
Hematologic improvement: 7%, 67% RBC/platelet
transfusion independent
Fili et al, Clin Cancer Research 2013, and Garcia-Manero, et al JCO 2013
“Lower Risk” MDS Has Poor Outlook
Post-HMA
Jabbour et al. Cancer. 2015.
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No Standard Approach to Post-HMA
Therapy in MDS• For healthy, fit patients:
– Intensive chemotherapy, SCT
• Majority of MDS patients are not candidates for intensive chemotherapy or stem cell transplant
• Large phase III trial: rigosertib (Estybon®) vs best supportive care– OS: 8.2 months vs 5.8 months (p=0.27)
• Effective treatment after HMA therapy is an unmet need in MDS
• Consider clinical trials when possible!Manero et al, Lancet Oncol. 2016 Apr;17(4):496-508.
Myelodysplastic Syndrome (MDS)The Pharmacist’s Role in Treatment and
Side Effects Management
Peter Campbell, PharmD, BCOPClinical Pharmacy Manager, Hematology/Oncology
Columbia University Irving Medical CenterNew York, NY
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Pharmacist
Role
Prior
Authorizations
Chemotherapy
Counseling
Dose
Modifications
Discharge
Preparation
Medication Review Supportive Care
Chemotherapy
Selection
Dose
Modifications
Toxicity Checks
Patient
Counseling
Antibiotic
Recommendations
Therapeutic Drug
Monitoring
Patient Case
• JM is a 78-year-old male with a past medical history of hypertension (HTN), hyperlipidemia (HLD), non-insulin dependent diabetes, COPD, and single knee replacement in 2016 who presents to the clinic after a month of increasing fatigue and easy bruising. JM’s labs resulted with a WBC of 4.1, ANC of 800, hemoglobin of 8.1, and platelet count of 210,000. A bone marrow biopsy was performed which was consistent with MDS with 3% immature myeloid cells, no mutations identified, del(5q) present
• What would be the preferred therapy for this patient?
• SubQ: 5–7 days per week • Granules: sprinkle on soft food immediately prior to administration, on an empty stomach or with light meal
• Tablets: take with water or other liquids, on an empty stomach or with light meal
• Tablets for suspension: make an oral suspension using water, apple juice, or orange juice, stirred to a fine foam. Take at least 30 minutes prior to food.
*Please refer to product-specific prescribing information for full administration instructions
Adverse effects
• Infusion site reactions• Hearing abnormalities• Visual disturbances
• Upset stomach• Nephrotoxicity• Hepatotoxicity• GI hemorrhage
Other information
• Topical anesthetics or corticosteroids can be used for injection site reactions
• Contraindicated in high-risk MDS
Leuk Res. 2015;39(10):1028-33.
Jadenu (deferasirox) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; December 2018.
Desferal (deferoxamine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; April 2018.
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Erythropoiesis-Stimulating Agents
• Although these agents are used in this setting, they do not alter the natural course of the disease– Studies have shown that there is not an increased risk of
progression to acute myeloid leukemia
• Patients that will have the best response are those with low baseline erythropoietin (EPO) levels– Typically response is greatest when EPO <500 units/L
• A hemoglobin of 10–12 g/dL should be targeted to reduce transfusions– Do NOT try to target a hemoglobin >12 g/dL
• In 2017 the FDA removed the Risk Evaluation and Mitigation Strategy (REMS) program for both darbepoetin alfa (Aranesp®) and epoetin alfa (Epogen®, Procrit®)
• In select scenarios, the use of G-CSF may improve the efficacy of erythropoiesis-stimulating agents
NCCN. Myelodysplastic Syndromes Guidelines. Version 2.2019.
Erythropoiesis-stimulating agents
Epoetin Alfa
(Epogen®, Procrit®)
• Dosing
– 150 – 300 units/kg SubQ
TIW
• Pharmacokinetics
– Onset: 10 days
– Peak: 2 – 6 weeks
– Half-life: 16 – 67 hours
Darbepoetin Alfa
(Aranesp®)
• Dosing
– 150 – 300 mcg SubQ once
weekly OR 500 mcg every
2 – 3 weeks
• Pharmacokinetics
– Onset: 2 – 6 weeks
– Half-life: approximately 3
times longer than epoetin
Data suggests that darbepoetin and epoetin have similar efficacy, with darbepoetin possibly resulting in improved outcomes due to the prolonged half-life
• Agents in this class increase hypomethylation of DNA, which allows normal gene differentiation and proliferation to be restored
• Azacitidine (Vidaza®) and decitabine (Dacogen®) are generally thought of as equally efficacious for treatment outcomes– Azacitidine has shown improved survival in high-risk patients with
MDS, and may be preferred in this setting
• Patients should receive 4 – 6 courses of therapy prior to determining treatment failure– Patients that are responding to therapy should continue to receive
treatment until no longer responsive
– Dosing frequency can be extended if treatment-related toxicities occur
NCCN. Myelodysplastic Syndromes Guidelines. Version 2.2019.
Azacitidine (Vidaza®)
• Dosing– 75 mg/m2/day for 7 days every 4 weeks
• May be given Mon – Fri, rest Sat/Sun, and completed Mon – Tues
• Administration– Must be infused within 1 hour of reconstitution due to stability
Blood cancers can develop in many different places within normal blood cell formation.The type of blood cancer that results has to do with where normal cell development is blocked.
This picture shows the cell type where different blood cancers arise.
• Chronic lymphocytic leukemia (CLL)
• B-cell non-Hodgkin lymphoma
• Hairy cell leukemia
• Hodgkin lymphoma
• T-cell non-Hodgkin lymphoma
• T-cell large granular lymphocytic (LGL) leukemia
• NK-cell non-Hodgkin lymphoma
• NK-cell large granular lymphocytic (LGL) leukemia
Neutropenia• Provide education related to signs and symptoms
of infection
• When to call the office; when to go immediately to the emergency room
• Prophylactic antimicrobials (NP)
• Neutropenic precautions (eg, good hand-washing, avoiding sick contacts)
• Growth factors (NP)
Anemia
• Provide education regarding signs and symptoms of anemia
• Fatigue is the most commonly reported symptom in patients with anemia
• Red cell growth factors (NP)
• When to transfuse
• Transfusion complications: infusion reaction, development of antibodies
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Thrombocytopenia
• Provide education regarding signs and symptoms of bleeding, lifestyle changes
• Identification of when transfusion is indicated
• Transfusion complications: infusion reaction, development of antibodies
Fatigue• One of the most difficult side effects to treat
– Blood is not always the answer
– Encouraging light exercise (eg, walking)
– Listening to your body
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Gastrointestinal Toxicity
• Nausea: Identify and treat EARLY!
– Side effect of specific treatments
– Choosing an antiemetic (NP)
• Constipation: Identify and treat EARLY!
– Side effect of specific treatments
– Prevention vs treatment
• Diarrhea: Identify and treat EARLY!
– Side effect of specific treatments
– Electrolyte imbalances
– Test for infectious process before treating
Poor Appetite
– Identify if it is poor appetite or nausea
– High calorie foods
– High protein foods
– Maximizing every bite
– Grazing
– Nutrition consult
– Medical marijuana
– Mirtazapine/Quetiapine
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Treatment Goals
• Clarification of goals of therapy – Depends on stage of disease and age/comorbidities– Transfusion independence – Prevent transformation to AML
• Ongoing discussion of disease status and treatment updates
• Minimize/manage toxicities • Improve/maintain quality of life • Collaboration with clinical trial staff• “New normal”
Biopsychosocial Approach to Care
• Psychological:
– Act as a confidant for patients and liaison to multidisciplinary team
– Emotional support for patients and their caregivers
– Identifying stressors and assisting with management
– Mental health referrals: the earlier the better
– Addressing and collaboration to increase adherence to medications (including oral chemotherapy drugs as well as supportive medications)
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Biopsychosocial Approach To Care
• Social:
– Loss of job, autonomy, daily routine
– Change of role in family unit and in other arenas
– Appropriate referrals to organizations for support
– Referral to social work
Overview of Nursing Role• Take into consideration the “whole” person
• Partner with patient and caregivers to promote optimal care with mutual understanding of goals
• Communicate in ways that meet the patient and caregivers where they are
• Use terms that everyone in the room understands
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The Social Worker’s Role• Establish therapeutic relationship with social worker early on
– Counseling for patient and support network throughout care
– Exploring impact of the “new normal”
» Sword of Damocles
– Access to durable medical equipment to assist with ADLs
– Referral to appropriate support groups, organizations
– Financial assistance for copays, medication, loss of income
Revisiting Case Study: JM
JM is a 78-year-old male with a past medical history of hypertension (HTN), hyperlipidemia (HLD), noninsulin-dependent diabetes, COPD, and single knee replacement in 2016 who presents to the clinic after a month of increasing fatigue and easy bruising. JM’s labs resulted with a WBC of 4.1, ANC of 800, hemoglobin of 8.1, and platelet count of 210,000. A bone marrow biopsy was performed that was consistent with MDS with 3% immature myeloid cells, no mutations identified, Del5q present
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What is Significant in This Case When Thinking About Next Steps From a
Nursing and Social Work Perspective?
• Biological: age, comorbidities, neutropenia and thrombocytopenia, performance status, staging
• Not addressed in case, but also important:
– Psychological: What is the state of their mental health? Do they have adequate coping skills? How likely are they to be able to adhere to various treatment regimens?
– Social: What is their QOL like now? What kind of caregiver support do they have? What kind of financial support might they need for various treatments?
Communication
• Education
• Trust
• Collaboration
• Mutual goals
• Ongoing conversations
• Biological, psychological, and social support
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Tying It All Together
• Reinforce patient and caregiver teaching with each visit
• Identify biological, psychological, and social factors that play into patient’s care and plan
• Ensure patient goals are in line with therapy prescribed
• Encourage questions to promote ongoing education and conversation
Summary
• Nurses, nurse practitioners, and social workers are in the unique role of addressing the multifaceted experience of being treated for MDS
• Education is a key responsibility and piece of the relationship
• Management of side effects, both from disease and treatment, is a priority
• Assess the “whole person” in order to fully address patient needs from diagnosis and throughout treatment
• Ongoing communication re: treatment and treatment goals with patients and caregivers
• Serve as a liaison to other members of the multidisciplinary team to ensure holistic approach to care
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RESOURCES FOR YOU & YOUR PATIENTS
FROM THE LEUKEMIA & LYMPHOMA SOCIETY (LLS)
WWW.LLS.ORG
LLS RESOURCES FOR HEALTHCARE PROFESSIONALS
Online and in-person CE/CME webinars, symposia & rounds
Free CME & CE www.LLS.org/CE
Podcast series for healthcare professionals
Conversations with experts about diagnosing &
treating blood cancers www.LLS.org/HCPpodcast
HCP palm card – User friendly links to resources for you & your patients