CARTITUDE-2: Efficacy of BCMA CAR T-cell Therapy in Progressive MM

Cilta-cel, a CAR T-cell treatment, expresses two BCMA-targeting, single-domain antibodies for avidity. The multicohort, phase 2 CARTITUDE-2 research is looking at how safe and effective cilta-cel is for multiple myeloma (MM) patients in different clinical settings and how it can be given outside of a hospital. Initial Cohort A results are shown here. Cohort A patients had progressive MM following 1–3 lines of treatment (LOT), comprising a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide-refractory and had no BCMA-targeting chemical exposure. A single cilta-cel infusion (target dose: 0.75×10⁶ CAR+ viable T cells/kg) was administered 5–7 days following lymphodepletion (daily cyclophosphamide [300 mg/m²] and fludarabine [30 mg/m²] for 3 d) and MRD 10-5 negativity. Safety (per CTCAE; CRS and ICANS by ASTCT) and secondary outcomes were response rates (IMWG).

A total of 20 patients (65% male; median age 60 years [38–75]) received cilta-cel as of February 2021 (median follow-up: 5.8 months [mo]; range: 2.5–9.8 mos). One patient was treated, outpatient. About 12 points < 3 prior lines, and eight had three prior LOTs. All patients received PI, IMiD, dexamethasone, 95% alkylating agents, and 65% daratumumab. About 95% were refractory to the final lot; 40% tripled. 95% (95% CI: 75–100) responded, 75% (95% CI: 51–91) attained severe CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. The median first response was 1.0 mo (0.7–3.3), and the median best response was 1.9 mo (0.9–5.1). The median response time was not attained. All four patients having MRD-evaluable samples at the 105 data cutoff were MRD-negative. 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) were hematologic AEs. Around 10% were in grade 3/4, and 85% had CRS. CRS onset took seven days (5–9) and lasted 3.5 days (2–11). 20% of grade 1/2 patients had CAR T-cell neurotoxicity. Three patients had ICANS (1 gr 1; 2 gr 2); the median time to onset was 8 d (7–11), and the median duration was 2 d (1–2). One patient developed Grade 2 facial paralysis with a 29-day start and 51-day duration. Investigators determined one COVID-19-related death. Outpatient safety was manageable. The study concluded that MM patients with 1–3 prior LOTs responded well to a single phase 2 cilta-cel infusion. Updated efficacy and safety, findings will determine outpatient treatment suitability in this and additional CARTITUDE-2 cohorts in the CARTITUDE-4 research.

Source: https://meetings.asco.org/abstracts-presentations/195446

Clinical Trial: http://clinicaltrials.gov/show/NCT04133636

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/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/J Clin Oncol 39, 2021 (suppl 15; abstr 8013) DOI 10.1200/JCO.2021.39.15_suppl.8013