3 miguel g pneumonitis esmo-preceptorship-meeting-case · esmo preceptorship programme...
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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
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ESMO PRECEPTORSHIP PROGRAMME
Conflicts of interest
� None. I declare that there are no financial conflicts
of interest with regard to this work
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ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� Woman, seventyyears old
� PS= 1
� Current smoker
� Diagnosis of lungadenocarcinoma stage IVA in 2013
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ESMO PRECEPTORSHIP PROGRAMME
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)
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ESMO PRECEPTORSHIP PROGRAMME
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
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ESMO PRECEPTORSHIP PROGRAMME
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
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ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� October 2017:
pneumonitis
– Asymptomatic
– Radiation pneumonits?
– ICIs are suspended
– Methylprednisolone 1mg /
kg / day
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ESMO PRECEPTORSHIP PROGRAMME
Clinical case
� Symptoms rapidly
progressed during the 2
weeks after the
diagnosis:
– Fever
– Shortness of breath
� She was admitted to
Medical Oncology Unit
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ESMO PRECEPTORSHIP PROGRAMME
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ESMO PRECEPTORSHIP PROGRAMME
Clinical case
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ESMO PRECEPTORSHIP PROGRAMME
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
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ESMO PRECEPTORSHIP PROGRAMME
Images
Week 1 Week 3 Week 4
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ESMO PRECEPTORSHIP PROGRAMME
Histopathology
Chronic restrictive pulmonary disease of morphological pattern type: Nonspecific interstitial pneumonia (NSIP), with bilateral diffuse pulmonary involvement.
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ESMO PRECEPTORSHIP PROGRAMME
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?
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ESMO PRECEPTORSHIP PROGRAMME
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
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ESMO PRECEPTORSHIP PROGRAMME
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
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ESMO Preceptorship Programme
Thanks for your attention!