Nikhil C. Munshi, MD of Dana-Farber Cancer Institute discusses ASCO20 Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results.
In triple-class exposed patients with RRMM (pts) progressing on immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and antibodies to CD38 (mAbs), the findings are poor. In Phase I CRB-401 research (NEJM2019;380:1726), Ide-cel, a BCMA targeted CAR T cell therapy, showed promising tolerability and efficacy in RRMM pts. Primary efficacy and safety results from the seminal phase II KarMMa studies of ide-cel in RRMM (NCT03361748) are presented.
Enrolled pts had 3 previous regimens (including IMiD, PI, and CD38 mAb) and were refractory according to IMWG guidelines to their last regimen. Pts received 150-450 ⁇ 106 CAR+ T cells (target dose range) after lymphodepletion (cyclophosphamide 300 mg / m2 + fludarabine 30 mg / m2 x 3). Overall response rate (ORR; primary), complete response (CR) rate, response length (DoR), and PFS were included in the endpoints.
Of the 140 pts that were enrolled, 128 got an ide-cel. The median age was 61 years; the median number of previous regimens was 6; 84% were triple- and 26% were penta-refractory. Most pts had bridging therapy (88 percent). The median follow-up at data cutoff (16 Oct 2019) was 11.3 mo. ORR was 73 percent and 8.6 mo of median PFS; both increased with a higher dose (Table). All subgroups, including older and high-risk pts, had an ORR around 50%. The most common toxicity of any grade (Gr) was cytopenia (97%) and cytokine release syndrome (CRS; 84%). CRS was primarily Gr 1/2; 5 pts (5%) had Gr 3, 1 had Gr 4, and 1 had Gr 5 (300 about 106). In 23 pts (18 percent), neurotoxicity developed; in 4 (3 percent) Gr 3 and 0 Gr 4. The median peak expansion of CAR+ T cells occurred at 11 d. In responders and parameters (AUC0-28d, Cmax), expansion was higher and increased with higher dose, with overlap of exposure across doses. Persistence was long term, with CAR+ T cells detected at 6 and 12 mo in 29/49 (59 percent) and 4/11 pts (36 percent).
In highly pre-treated RRMM pts, Ide-cel showed deep, durable responses. Efficacy and safety reflect previous reports and promote a favorable profile of ide-cel clinical benefit-risk across the target dose range. Information regarding clinical trials: NCT03361748.