Director of Myeloma Service Tel- Aviv Sourasky (Ichilov) Medical Center, and Faculty of health Science, Tel Aviv University, Tel Aviv, Israel Tel Aviv, Israel
Introduction: Although anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy proved unprecedented efficacy in patients with relapsed/refractory (R/R) multiple myeloma (MM), its availability remains limited. HBI0101 is a novel second generation optimized anti-BCMA CART, that was developed in an academic setting. The phase I study evaluating HBI0101 (NCT04720313) demonstrated manageable safety and high efficacy. Here we present the updated results for the patients who received the recommended phase II target dose (RP2D) of 800x10^6 CART cells.
Methods: The patients enrolled had R/R MM with at least 3 prior lines of therapy, including a PI, IMiD and anti CD38 antibody. Inclusion criteria were relatively permissive as compared with other CART clinical trials, including thresholds of 30x109/ml platelets, creatinine clearance of 20ml/min and performance status of < 2 by ECOG scale.
Results: 84 patients with a median of 4 prior lines (range 3-13) were infused with the RP2D, most (73/84, 87%) were triple refractory, 32/84 (38%) were penta-refractory and 14/84 (17%) had received prior anti-BCMA therapy. 22/84 (26%) had extra-medullary disease, 33 of 81 (41%) had high-risk cytogenetics (t(4:14)/t(14:16)/del17), and 61/81 (75%) including 1Q gain. Of note: 48% would not have met the inclusion criteria for the registrational trials of approved anti-BCMA CART therapy.
The overall response rate and complete response (CR)/stringent CR rates were 77/84 (92%) and 46/84 (55%), respectively, with 62/84 (74%) achieving minimal residual disease negativity at day +30. With a median follow-up of 12 months (range 4-30), the median progression-free survival was 11.6 months (95% CI: 8.6-14.6) and the median overall survival was not reached (NR) (95% CI: 19.6-NR).
Safety was manageable with grade 3-4 hematological toxicities common (anemia -62%, thrombocytopenia- 42%, neutropenia- 99%). Cytokine release syndrome (CRS) occurred in 80/84 (95%), including 16 patients with grade 3 CRS (19%), but no cases of grade 4/5. Neurological toxicity was rare and mild (3 cases, all of grade 1-2). No irreversible organ toxicities or treatment related deaths occurred.
Conclusions: HBI0101 BCMA CART results demonstrate the high efficacy and manageable safety in a frailer and higher risk population as compared with the registrational studies of commercial products. This data not only support further utilization of HBI0101 CART therapy, but also supports CART production at an academic setting in general, ensuring a sufficient CART supply in the light of the increasing demand.
