CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy.

Mounzer E. Agha UPMC Hillman Cancer Center, Pittsburgh, PA info_outline Mounzer E. Agha, Adam D. Cohen, Deepu Madduri, Yael C. Cohen, Michel Delforge, Jens Hillengass, Hartmut Goldschmidt, Katja Weisel, Marc-Steffen Raab, Christof Scheid, Jordan Mark Schecter, Kevin C. De Braganca, Helen Varsos, Liwei Wang, Martin Vogel, Marlene Carrasco-Alfonso, Muhammad Akram, Xiaoling Wu, Tonia Nesheiwat, Hermann Einsele

Authors Mounzer E. Agha UPMC Hillman Cancer Center, Pittsburgh, PA info_outline Mounzer E. Agha, Adam D. Cohen, Deepu Madduri, Yael C. Cohen, Michel Delforge, Jens Hillengass, Hartmut Goldschmidt, Katja Weisel, Marc-Steffen Raab, Christof Scheid, Jordan Mark Schecter, Kevin C. De Braganca, Helen Varsos, Liwei Wang, Martin Vogel, Marlene Carrasco-Alfonso, Muhammad Akram, Xiaoling Wu, Tonia Nesheiwat, Hermann Einsele Organizations UPMC Hillman Cancer Center, Pittsburgh, PA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, Mount Sinai Medical Center, New York, NY, Tel-Aviv Sourasky (Ichilov) Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, Universitaire Ziekenhuizen Leuven, Leuven, Belgium, Roswell Park Comprehensive Cancer Center, Buffalo, NY, University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, University Hospital Heidelberg, Heidelberg, Germany, University of Cologne, Cologne, Germany, Janssen R&D, Raritan, NJ, Janssen Global Services, LLC, Raritan, NJ, Legend Biotech USA, Inc, Piscataway, NJ, Legend Biotech USA, Inc, Somerset, NJ, Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Janssen Research & Development, LLC, Pharmaceutical/Biotech Company Background: Cilta-cel is a CAR T-cell therapy expressing two BCMA-targeting, single-domain antibodies designed to confer avidity. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for patients (pts) with MM and exploring suitability of outpatient administration. Here, we present initial results from Cohort A. Methods: Cohort A pts had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×10 6 CAR+ viable T cells/kg) was given 5–7 days (d) after start of lymphodepletion (daily cyclophosphamide [300 mg/m 2 ] and fludarabine [30 mg/m 2 ] for 3 d). The primary objective was minimal residual disease (MRD) 10 -5 negativity. Secondary outcomes were response rates (IMWG) and safety (per CTCAE; CRS and ICANS by ASTCT). Results: As of Feb 2021 data cutoff (median follow-up: 5.8 months [mo]; range: 2.5–9.8 mos), 20 pts (65% male; median age 60 years [38–75]) received cilta-cel; 1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (1–3); 12 pts received < 3 prior lines and 8 received 3 prior LOT. All pts were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT; 40% were triple refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 mo (0.7–3.3); median time to best response was 1.9 mo (0.9–5.1). Median duration of response was not reached. All pts (n = 4) with MRD-evaluable samples at 10 -5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%; gr 3/4: 90%), thrombocytopenia (80%; gr 3/4: 35%), anemia (65%; gr 3/4: 40%), lymphopenia (60%; gr 3/4: 55%), and leukopenia (55%; all gr 3/4). CRS occurred in 85% of pts; 10% were gr 3/4. Median time to CRS onset was 7 d (5–9), with a median duration of 3.5 d (2–11). CAR T-cell neurotoxicity occurred in 20% of pts (all gr 1/2). Three pts had ICANS (1 gr 1; 2 gr 2); median time to onset was 8 d (7–11) and median duration was 2 d (1–2). One pt had gr 2 facial paralysis; time to onset was 29 d with a duration of 51 d. One death occurred due to COVID-19 (assessed as treatment (tx)-related by investigator). Safety profile was manageable in the pt treated in an outpatient setting. Conclusions: A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in pts with MM who had 1–3 prior LOT. Updated efficacy and safety findings will inform suitability of outpatient tx in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study. Clinical trial information: NCT04133636