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MM-183 CARTITUDE-2 Cohort A: Updated Clinical Data and Biological Correlative Analyses of Ciltacabtagene Autoleucel (cilta-cel) in Lenalidomide-Refractory Patients With Progressive Multiple Myeloma (MM) After 1–3 Prior Lines of Therapy (LOT)

Hillengass J, Cohen AD, Delforge M, Einsele H, Goldschmidt H, Weisel K, Raab MS, Scheid C, Schecter JM, de Braganca KC, Varsos H, Yeh Tm, Mistry P, Roccia T, Corsale C, Akram M, Pacaud L, Nesheiwat T, Agha M, Cohen YC (2022)

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Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 22

Pages Range: S411-

DOI: 10.1016/S2152-2650(22)01600-7

Abstract

Context: CARTITUDE-2 (NCT04133636) Cohort A is assessing cilta-cel in lenalidomide-refractory patients with progressive MM after 1–3 prior LOT. Objective: To present updated results from CARTITUDE-2 Cohort A. Design: Phase 2, multicohort study. Patients: Lenalidomide-refractory patients with progressive MM after 1–3 prior LOT (PI and IMiD included) and no previous exposure to BCMA-targeting agents. Interventions: Single cilta-cel infusion (target dose 0.75×10⁶ CAR+ viable T-cells/kg) after lymphodepletion Main Outcome Measures: Primary endpoint was minimal residual disease (MRD) negativity at 10^-5. Management strategies were used to reduce risk of movement/neurocognitive adverse events (MNTs). Pharmacokinetics (PK) (Cmax/Tmax of CAR+T-cell transgene levels), cytokine release syndrome (CRS)-related cytokines over time, peak cytokine levels by response/CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+T-cell CD4/CD8 ratio by response/CRS/ICANS are being evaluated. Results: As of January 2022 (median follow-up [MFU] 17.1 months), 20 patients (65% male; median age 60 years; median 2 prior LOT; 95% refractory to last LOT) received cilta-cel. Overall response rate was 95% (90% ≥complete response; 95% ≥very good partial response). Median times to first and best response were 1.0 month and 2.6 months, respectively. All 16 MRD-evaluable patients achieved MRD negativity at 10^-5. Median duration of response was not reached. At 12 months, event-free rate was 79% and progression-free survival rate was 75%. 95% of patients had CRS (gr3/4 10%); median time to onset was 7 days and median duration was 3 days. Neurotoxicity was reported in 30% of patients (5 gr1/2; 1 gr3/4) and ICANS in 15% (all 3 gr1/2); 1 patient had gr2 facial paralysis. No MNTs were observed. 1 death occurred due to COVID-19 (treatment-related), 2 due to progressive disease, and 1 due to sepsis (not treatment-related). Preliminary PK analyses showed peak CAR-T cell expansion at day 10.5; median persistence was 153.5 days. Conclusions: At MFU of 17.1 months, a single cilta-cel infusion resulted in deep and durable responses in lenalidomide-refractory MM patients with 1–3 prior LOT. We will present updated PK/cytokine/CAR-T subset analyses and clinical correlation to provide novel insights into biological correlates of efficacy/safety in this population.

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How to cite

APA:

Hillengass, J., Cohen, A.D., Delforge, M., Einsele, H., Goldschmidt, H., Weisel, K.,... Cohen, Y.C. (2022). MM-183 CARTITUDE-2 Cohort A: Updated Clinical Data and Biological Correlative Analyses of Ciltacabtagene Autoleucel (cilta-cel) in Lenalidomide-Refractory Patients With Progressive Multiple Myeloma (MM) After 1–3 Prior Lines of Therapy (LOT). Clinical Lymphoma, Myeloma and Leukemia, 22, S411-. https://dx.doi.org/10.1016/S2152-2650(22)01600-7

MLA:

Hillengass, Jens, et al. "MM-183 CARTITUDE-2 Cohort A: Updated Clinical Data and Biological Correlative Analyses of Ciltacabtagene Autoleucel (cilta-cel) in Lenalidomide-Refractory Patients With Progressive Multiple Myeloma (MM) After 1–3 Prior Lines of Therapy (LOT)." Clinical Lymphoma, Myeloma and Leukemia 22 (2022): S411-.

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