PT  - JOURNAL ARTICLE
AU  - Marcela Carausu
AU  - Arnaud Beddok
AU  - Adriana Langer
AU  - Nicolas Girard
AU  - François-Clément Bidard
AU  - Marie-Ange Massiani
AU  - Damien Ricard
AU  - Luc Cabel
TI  - Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature
AID  - 10.1186/s40425-019-0803-x
DP  - 2019 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 317
VI  - 7
IP  - 1
4099  - http://jitc.bmj.com/content/7/1/317.short
4100  - http://jitc.bmj.com/content/7/1/317.full
SO  - J Immunother Cancer2019 Dec 01; 7
AB  - Background Neurologic complications as myelitis are very rare but extremely deleterious adverse effects of both immunotherapy and radiotherapy. Many recent studies have focused on the possible synergy of these two treatment modalities due to their potential to enhance each other’s immunomodulatory actions, with promising results and a safe tolerance profile.Case presentation We report here the case of a 68-year-old man with metastatic non-small-cell lung cancer (NSCLC) who developed myelitis after T12-L2 vertebral radiotherapy, with motor deficit and sphincter dysfunction, while on treatment with pembrolizumab (an immune checkpoint inhibitor). The spinal abnormalities detected by magnetic resonance imaging (MRI), suggestive of myelitis, faithfully matched the area previously irradiated with 30 Gy in 10 fractions, six and a half months earlier. After immunotherapy discontinuation and steroid treatment, the patient rapidly and completely recovered. On progression, pembrolizumab was rechallenged and, after 8 cycles, the patient is on response and there are no signs of myelitis relapse.Conclusion The confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy was not rechallenged. The occurrence of a radiation recall phenomenon, in this case, can not be excluded, and radiation recall myelitis has already been described with chemotherapy and targeted therapy. Safe rechallenges with the incriminated drug, even immunotherapy, have been reported after radiation recall, but we describe it for the first time after myelitis.Abbreviations:ALKAnaplastic lymphoma kinaseCNSCentral nervous systemCTComputed tomographyCTLA-4Cytotoxic T-lymphocyte antigen-4DRMDelayed radiation myelopathyEGFREpidermal growth factor receptorGyGrayICIImmune checkpoint inhibitorIL-6Interleukin-6LQED2Linear-Quadratic Equivalent Dose at 2 Gy per fractionMRIMagnetic resonance imagingNOSNitric oxide synthaseNSCLCNon-small-cell lung cancerPD-1Programmed cell death protein-1PD-L1Programmed death-ligand 1TNFαTumor necrosis factor alphaVEGFVascular endothelial growth factor