P-026: Safety and efficacy of a locally produced novel anti-BCMA chimeric antigen receptor T-cell (CART) (HBI0101) for the treatment of relapsed and refractory multiple myeloma

Introduction: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101 is a novel second generation optimized anti-BCMA CART, that was developed in an academic setting. The phase Ia study evaluating HBI0101 (NCT04720313) proved manageable safety profile and initial high efficacy (Asherie, Haematologica 2022). Here we present the updated phase 1a results as well as the phase 1b results including 50 patients treated to date.

Methods: At Hadassah Medical Center we have developed a new anti-BCMA CAR T with 4-1BB co-stimulatory domain (HBI0101) for the treatment of R/R MM. Following phase 1a study, evaluating the first 20 R/R MM patients with three or more prior lines of therapy, including a PI, IMiD and anti CD38 antibody (infusing 150x10^6 (n=6), 450x10^6 (n=7) and 800x10^6 (n=7) CAR T cells), the phase Ib study further evaluated the infusion of 800x10^6 CAR T cells.

Results: Fifty R/R MM patients were included in the phase Ia and Ib cohorts. The median number of prior lines was 5 (3-13) and most (92%) were triple refractory to PI, IMiDs and anti-CD38 antibodies. 30% were penta-refractory and 30% were refractory to belantamab mofadotin.
Safety was manageable with grade 3-4 hematological toxicities common (anemia - 54%, thrombocytopenia - 60%, neutropenia & lymphopenia- 100%). Cytokine release syndrome (CRS) occurred in 46/50 (92%), but were mostly (41/46) of grade 1-2, and manageable with frequent use of tocilizumab (70%). No immune effector cell associated neurotoxicity syndrome (ICANS) cases were observed, and no irreversible organ toxicities or treatment related deaths occurred.
The overall response rate (ORR) of the established 800x10^6 CAR T cells was 87%. Of 37 patients treated with this dose, 21 (57%) achieved complete response (CR)/stringent CR, and 27 (73%) achieved minimal residual disease (MRD) negativity at day +30. At data cutoff, with a median follow-up of 6 months (range 1-17.4), the median progression-free survival was 11 months and the median overall survival was not reached. Although the presence of extra-medullary disease and prior anti-BCMA therapy correlated with worse outcome, high response rates were still observed (ORR of 96%/63% for patients without/with extra-medullary disease, respectively, and 93%/73% for patients without/with prior anti-BCMA therapy, respectively).

Conclusions: Our findings demonstrate the manageable safety and high efficacy profiles of HBI0101, comparable to those reported of commercial anti-BCMA CART products. These favorable data are encouraging and support decentralization of CART production at an academic setting, ensuring a sufficient CART supply in the light of the increasing local demand.