Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies

Adam D. Cohen, Samir Parekh, Bianca D. Santomasso, Jaime G. llego Pérez-Larraya, Niels W. C. J. van de Donk, Bertrand Arnulf, Maria-Victoria Mateos, Nikoletta Lendvai, Carolyn C. Jackson, Kevin C. de Braganca, Jordan M. Schecter, Loreta Marquez, Erin Lee, Ingrid Cornax, Enrique Zudaire, Claire Li, Yunsi Olyslager, Deepu Madduri, Helen Varsos, Lida PacaudMuhammad Akram, Dong Geng, Andrzej Jakubowiak, Hermann Einsele, Sundar Jagannath

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Abstract

Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit–risk profile for treatment of MM.

Original languageEnglish
Article number32
JournalBlood Cancer Journal
Volume12
Issue number2
DOIs
Publication statusPublished - 1 Feb 2022

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