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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.
Immune checkpoint inhibitor (ICI) associated myelitis is a severe neurological complication. Prompt, aggressive combination immunotherapy is crucial for improving outcomes in patients with this rare condition.
Area of Science:
- Neuroimmunology
- Oncology
- Pharmacovigilance
Background:
- Immune checkpoint inhibitors (ICIs) are increasingly used in cancer therapy.
- Neurological adverse events, including myelitis, can occur with ICI treatment.
- Understanding the characteristics and outcomes of ICI-associated myelitis is critical for patient management.
Purpose of the Study:
- To define the clinical characteristics and outcomes of myelitis associated with immune checkpoint inhibitors (ICIs).
Main Methods:
- Retrospective analysis of French Pharmacovigilance Agency and OncoNeuroTox network databases (2011-2020).
- Systematic literature review to identify additional cases.
- Clinical, neuroimaging (MRI), and cerebrospinal fluid (CSF) data were analyzed.
Main Results:
- Seven patients developed myelitis after ICI treatment (anti-PD1 or anti-PD1 + anti-CTLA4).
- Common symptoms included paraparesis, sphincter dysfunction, and sensory disturbances; all patients were nonambulatory at peak severity.
- MRI showed longitudinally extensive lesions; CSF revealed inflammation. Concomitant neurological involvement was frequent.
- Despite prompt treatment with glucocorticoids, 5/7 patients required second-line immunotherapy due to poor recovery or relapse.
- Only 3/7 patients regained ambulatory status at last follow-up.
Conclusions:
- Myelitis is a rare but severe complication of ICIs with limited response to glucocorticoids alone.
- Longitudinally extensive myelitis associated with ICIs often leads to poor functional outcomes.
- Aggressive and prolonged combination immunotherapy strategies are likely necessary upfront to improve patient outcomes and prevent relapses.
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