Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results.

Abstract

8503 Background: Outcomes are poor in triple-class exposed RRMM patients (pts) who progress on immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and CD38 antibodies (mAbs). Ide-cel, a BCMA targeted CAR T cell therapy, showed promising tolerability and efficacy in RRMM pts in the phase I CRB-401 study ( NEJM2019;380:1726). We present primary efficacy and safety data from the pivotal phase II KarMMa trial of ide-cel in RRMM (NCT03361748). Methods: Enrolled pts had ≥3 prior regimens (including IMiD, PI, and CD38 mAb) and were refractory to their last regimen per IMWG criteria. After lymphodepletion (cyclophosphamide 300 mg/m2+ fludarabine 30 mg/m2 x 3), pts received 150─450 × 106 CAR+ T cells (target dose range). Endpoints included overall response rate (ORR; primary), complete response (CR) rate, duration of response (DoR), and PFS. Results: Of 140 pts enrolled, 128 received ide-cel. Median age was 61 y; median no. of prior regimens was 6; 84% were triple- and 26% were penta-refractory. Most pts (88%) had bridging therapy. At data cutoff (16 Oct 2019), median follow up was 11.3 mo. ORR was 73% and median PFS was 8.6 mo; both increased with higher dose (Table). All subgroups had an ORR ≥50%, including older and high-risk pts. Most common any-grade (Gr) toxicities were cytopenias (97%) and cytokine release syndrome (CRS; 84%). CRS was mainly Gr 1/2; 5 pts (5%) had Gr 3, 1 had Gr 4, and 1 had Gr 5 (at 300 × 106). Neurotoxicity developed in 23 pts (18%); 4 (3%) Gr 3 and 0 Gr ≥4. Median peak CAR+ T cell expansion occurred at 11 d. Expansion was higher in responders and parameters (AUC0−28d, Cmax) increased with higher dose, with exposure overlap across doses. Persistence was durable, with CAR+ T cells detected in 29/49 (59%) and 4/11 pts (36%) at 6 and 12 mo. Conclusions: Ide-cel demonstrated deep, durable responses in heavily pretreated RRMM pts. Efficacy and safety reflected prior reports and support a favorable ide-cel clinical benefit-risk profile across the target dose range. Clinical trial information: NCT03361748 . [Table: see text]

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time

“…The median OS was 19.4 months (95% CI, 18.2-NE). In this study, peak CAR T-cell expansion did correlate with clinical outcome, and cell expansion correlated with longer PFS in the higher dose levels [23].…”

“…CAR-T cell expansion and peak CAR-T cell levels do correlate with response across different trials [28,30,33]. In the KarMMa [23] study, peak ide-cel vector copies were significantly higher in responders as compared to non-responders, and a similar experience was published with the UPenn BCMA CAR T-cell [30]. However, recent data using cilta-cel in the phase 1b/2 CARTITUDE-1 study fail to show this correlation.…”

BCMA-targeted immunotherapy for multiple myeloma

“…One hundred seven (83.6%) patients encountered CRS including 7 (5.5%) grade ≥ 3 events and 1 death. Twenty-three (18%) patients encountered NTX including 4 (3.1%) grade ≥ 3 events [103].…”

Multiple Myeloma: An Overview of the Current and Novel Therapeutic Approaches in 2020

“…The first results with bb2121, from the phase 1 study CRB 401, showed an ORR of 85% with 45% CR in end-stage RRMM patients and a median PFS of 11.8 months [ 41 ]. These results led to the development of a phase 2 study, KarMMa1 [ 42 ]; most of the patients were heavily pre-treated (median of six previous treatments) and 84% were triple-class (IMiD, PI, anti-CD38 mAb) refractory. The ORR was 73%, including 33% CR, and median PFS was 8.8 months.…”