Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple Myeloma after 1-3 Prior Lines of Therapy: Updated Results from CARTITUDE-2

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.3866-3866
• Main Authors: Cohen, Yael C., Cohen, Adam D, Delforge, Michel, Hillengass, Jens, Goldschmidt, Hartmut, Weisel, Katja, Raab, Marc-Steffen, Scheid, Christof, Schecter, Jordan M., De Braganca, Kevin C., Varsos, Helen, Yeh, Tzu-min, Wang, Liwei, Vogel, Martin, Corsale, Christina, Akram, Muhammad, Pacaud, Lida, Nesheiwat, Tonia, Agha, Mounzer, Einsele, Hermann
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-146072

Introduction: There are several treatment options for patients (pts) with progressive multiple myeloma (MM) who are refractory to lenalidomide but most pts relapse shortly after receiving salvage treatment. Cilta-cel is a CAR-T therapy expressing 2 BCMA-targeting, single-domain antibodies that demonstrated early, deep, and durable responses in pts with MM who had received ≥3 prior lines of therapy (LOT) in the phase 1b/2 CARTITUDE-1 study (Berdeja, Lancet, 2021). The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for pts with MM and exploring suitability of outpatient administration. Initial analysis (median follow-up 5.8 mo) of pts in CARTITUDE-2 cohort A (lenalidomide-refractory with 1-3 prior LOT) demonstrated an overall response rate (ORR) of 95%, with 75% of pts achieving complete response or better (≥CR) and 85% achieving very good partial response or better (≥VGPR). Here, we present updated results for this population. Methods: Pts had progressive MM after 1-3 prior LOT, including a PI and immunomodulatory drug (IMiD), were lenalidomide-refractory, and had no prior exposure to BCMA-targeting agents. Bridging therapy was allowed after apheresis. A single cilta-cel infusion (target dose 0.75×10 6 CAR+ viable T cells/kg) was given 5-7 d after start of lymphodepletion (daily cyclophosphamide [300 mg/m 2] and fludarabine [30 mg/m 2] for 3 d). The primary endpoint was minimal residual disease (MRD) negativity at 10 -5. Secondary endpoints were ORR, duration of response (DOR), time and duration of MRD negativity, and incidence and severity of AEs. MRD was assessed by next-generation sequencing, response was assessed per IMWG criteria, and adverse events (AEs) were graded using CTCAEv5.0 (CRS and ICANS by ASTCT). Results: Initial results from this cohort were published at ASCO 2021 . Here we report data as of the April 15, 2021, data cutoff (median follow-up 9.7 mo: range 3.3-13.4) . 20 pts (65% male; median age 60 years [range 38-75]) received cilta-cel; 1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (range 1-3); 60% received 1 or 2 prior LOT and 40% received 3 prior LOT. All pts were exposed to a PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. In all, 95% of pts were refractory to the last LOT; 40% were triple-class refractory. ORR was 95% (95% CI 75.1-99.9); 85% (95% CI 62.1-96.8) of pts had ≥CR, and 9