PT  - JOURNAL ARTICLE
AU  - Picca, Alberto
AU  - Berzero, Giulia
AU  - Bihan, Kevin
AU  - Jachiet, Vincent
AU  - Januel, Edouard
AU  - Coustans, Marc
AU  - Cauquil, Cecile
AU  - Perrin, Julie
AU  - Berlanga, Pablo
AU  - Kramkimel, Nora
AU  - Garel, Bethsabée
AU  - Devic, Perrine
AU  - Ducray, François
AU  - Benazra, Marion
AU  - Bompaire, Flavie
AU  - Leclercq, Delphine
AU  - Michot, Jean-Marie
AU  - Ammari, Samy
AU  - Psimaras, Dimitri
TI  - Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors
AID  - 10.1212/NXI.0000000000000967
DP  - 2021 May 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e967
VI  - 8
IP  - 3
4099  - http://nn.neurology.org/content/8/3/e967.short
4100  - http://nn.neurology.org/content/8/3/e967.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 May 01; 8
AB  - Objective To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs).Methods We performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011–2020). A systematic review of the literature was performed to identify similar cases.Results We identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients.Conclusion Myelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses.CTLA4=cytotoxic T-lymphocyte-associated protein 4; ICI=immune checkpoint inhibitor; irAE=immune-related adverse event; NSCLC=non–small-cell lung cancer; PD-1=programmed death 1; PDL-1=programmed death-ligand 1