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Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors
Alberto Picca1, Giulia Berzero1, Kevin Bihan1
1From the Department of Brain and Behavioral Sciences (A.P., G.B.), University of Pavia, Italy; Regional Pharmacovigilance Center (K.B.), Department of Pharmacology, APHP; APHP (V.J., E.J.), Hôpital Saint-Antoine, Paris; CHI de Cornouaille (M.C.), Quimper; Service de Neurologie (C.C.), Hôpital Bicêtre, AP-HP, Le Kremlin-Bicetre; Hôpitaux Privés de Metz (J.P.), Metz; Gustave Roussy (P.B.), Université Paris-Saclay, Villejuif; Service de Dermatologie (N.K., B.G.), Cochin Hospital AP-HP, Paris; Centre Hospitalier Universitaire Lyon Sud (P.D.), Hospices Civils de Lyon, Pierre-Bénite; Hospices Civils de Lyon (F.D.), Hôpital Neurologique, Bron; Inserm (M.B.), CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière (ICM), Paris; OncoNeuroTox Group (F.B.), Hôpital Percy, Clamart; Service de Neuroradiologie (D.L.), AP-HP Pitié-Salpêtrière, Paris; Département d'Innovation Thérapeutique et d'Essais Précoces (J.-M.M.), Gustave Roussy, Villejuif; Department of Diagnostic Radiology (S.A.), Gustave Roussy, Villejuif; and Service de Neurologie 2 (D.P.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France.
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.
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