3 Miguel G Pneumonitis ESMO-Preceptorship-Meeting-Case · ESMO Preceptorship Programme Possibleimmune-relatedpneumonitisafter radiotherapy Miguel Garcia Pardo de Santayana Hospital

ESMO Preceptorship Programme

Possible immune-related pneumonitis after

radiotherapy

Miguel Garcia Pardo de Santayana

Hospital Gregorio Marañon, Madrid, Spain

Immuno-Oncology - Zurich (Glattbrugg), 2-3.11.2018

ESMO PRECEPTORSHIP PROGRAMME

Conflicts of interest

� None. I declare that there are no financial conflicts

of interest with regard to this work


Clinical case

� Woman, seventyyears old

� PS= 1

� Current smoker

� Diagnosis of lungadenocarcinoma stage IVA in 2013


Clinical case

� She received:

– Carboplatin + paclitaxel + bevacizumab. PFS 9months

– Carboplatin + pemetrexed. PFS 9months

– Vinorelbine. PFS 3months

– Nivolumab as fourth line treatment with Partial Response.

PFS 12months

– Docetaxel. PFS 3months

October 2016: Phase I/II Clinical Trial (ICIs combination)


Clinical case

� Started October 2016

� Stable disease. 12

cycles, until July 2017

(PFS 9 months).

� July 2017: palliative

thoracic radiotherapy

for minor local

progression, and

continue treatment


Clinical case

� Long survivor patient (> 4 years of advanced disease)

� Re-treatment with immunotherapy

� No extrathoracic metastases

� Palliative thoracic radiotherapy for control of local

progression in oligometastatic disease


Clinical case

� October 2017:

pneumonitis

– Asymptomatic

– Radiation pneumonits?

– ICIs are suspended

– Methylprednisolone 1mg /

kg / day


Clinical case

� Symptoms rapidly

progressed during the 2

weeks after the

diagnosis:

– Fever

– Shortness of breath

� She was admitted to

Medical Oncology Unit



Clinical case


Clinical case

� We rule out infectious causes (BAL cultures included)

� Covered with broadspectrum antibiotics

� High dose methylprednisolone

� We added Infliximab 5mg/kg iv with no improvement

� She finally died 4 weeks after the diagnosis of pneumonitis


Images

Week 1 Week 3 Week 4


Histopathology

Chronic restrictive pulmonary disease of morphological pattern type: Nonspecific interstitial pneumonia (NSIP), with bilateral diffuse pulmonary involvement.


Discussion

� Was thoracic radiotherapy the best option, or were

we too aggressive?

� Do you agree this is a immune-related

pneumonitis? Did the radiotherapy have a synergy

effect in the toxicity?

� What could we have done better? Is infliximab the

best option? Did we add infliximab too late?


Discussion

� Combination of immune checkpoint inhibitors and radiotherapy: abscopal effect?

– Radiotherapy (RT) is known to activate several key elements of the immune response and can prime the immune response2,3,4

– However, uncertainties remain regarding a potential synergy resulting in increased toxicities

– Effects of concomitant ICIs with thoracic radiotherapy on pulmonary toxicities is not currently known4

– A particular attention should be paid to the diagnosis and management of these new toxicities associated with immunotherapy specifically in association with radiotherapy4


References1. Haanen JBAG, Carbonnel F, Robert C, Kerr K, Peters S, Larkin J, Jordan K.

Management of toxicities from immunotherapy: ESMO Clinical Practice

Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2017; 28:

119-142

2. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint

blockade activate non-redundant immune mechanisms in cancer. Nature 2015;

520: 373–377

3. Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer

immunotherapy. JAMA Oncol 2015;1: 1325–1332.

4. Louvel G, Bahleda R, Ammari S, et al. Immunotherapy and pulmonary toxicities:

can concomitant immune-checkpoint inhibitors with radiotherapy increase the risk

of radiation pneumonitis? Eur Respir J 2018; 51: 1701737

ESMO Preceptorship Programme

Thanks for your attention!

3 Miguel G Pneumonitis ESMO-Preceptorship-Meeting-Case · ESMO Preceptorship Programme Possibleimmune-relatedpneumonitisafter radiotherapy Miguel Garcia Pardo de Santayana Hospital

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