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- Title
P-155: Incidence, mitigation, and management of neurologic adverse events in CARTITUDE-2, a phase 2 study of ciltacabtagene autoleucel (cilta-cel) in patients with Multiple Myeloma.
- Authors
Einsele, Hermann; Parekh, Samir; Madduri, Deepu; Santomasso, Bianca; Pérez-Larraya, Jaime Gállego; van de Donk, Niels W.C.J.; Arnulf, Bertrand; Mateos, María-Victoria; De Braganca, Kevin C.; Varsos, Helen; Carrasco-Alfonso, Marlene J.; Akram, Muhammad; Lendvai, Nikoletta; Jackson, Carolyn C.; Olyslager, Yunsi; Zudaire, Enrique; Li, Claire; Dong Geng; Jakubowiak, Andrzej; Cohen, Adam
- Abstract
CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficacy and safety of cilta-cel, a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen (BCMA)-targeting single-domain antibodies, in patients (pts) with multiple myeloma (MM) in various clinical settings. This report describes the mitigation and management strategies implemented to identify and reduce the risk for neurologic adverse events (AEs) in pts with progressive MM after 1–3 prior lines of therapy (Cohort A). Eligible pts (≥18 years) had MM, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive disease after 1–3 prior lines of therapy including a proteasome inhibitor and immunomodulatory drug, and were lenalidomide refractory (no prior BCMA-targeting agent). Cilta-cel was given as a single infusion at the targeted dose of 0.75×106 (range 0.5–1.0×106) CAR+ viable T cells/kg 5–7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). Monitoring and mitigation strategies for neurologic AEs included providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T-related immune effector cell-associated neurotoxicity syndrome (ICANS) using the ICE tool, handwriting assessments to detect micrographia, and brain MRI and electroencephalogram for pts with prior neurologic disease. Management strategies included evaluating infectious and paraneoplastic etiologies upon observation of ICANS ≥grade 1, administration of tocilizumab (if concurrent with cytokine release syndrome [CRS], all grades of ICANS) and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). ICANS and CRS were graded by American Society for Transplantation and Cellular Therapy criteria; non-ICANS neurotoxicities were graded per Common Terminology Criteria for Adverse Events, v5.0. As of 15 Jan 2021 (median follow-up: 5.8 months [2.5–9.8]), 20 pts (65% male, median age 60 years [38–75]) in Cohort A received cilta-cel. Four pts (20%) had neurotoxicities. Three pts had ICANS (grade 1/2) with median time to onset of symptoms of 8 days (7–11) and median duration of 2 days (1–2). Supportive measures to treat ICANS were received by 2/3 pts, including levetiracetam and steroids; 3/3 had concurrent CRS and all recovered. One pt developed isolated facial paralysis (grade 2); onset: Day 29 after cilta-cel infusion, recovered: 51 days after the onset following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported. In pts with MM, neurologic AEs were generally manageable following treatment with cilta-cel. With a median of 5.8 months of follow-up, no movement or neurocognitive disorders were reported in pts from Cohort A. These findings suggest that early detection and management of neurologic AEs can lead to better treatment outcomes.
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2021, Vol 21, pS120
- ISSN
2152-2650
- Publication type
Article
- DOI
10.1016/S2152-2650(21)02282-5