OA – 08: Safety and preliminary efficacy of BMS-986393, a GPRC5D CAR T cell therapy, in patients (pts) with relapsed/refractory (RR) multiple myeloma (MM) and 1–3 prior regimens: results from a phase 1 study
Associate Professor, Department of Hematology & Hematopoietic Cell Transplantation City of Hope Comprehensive Cancer Center Duarte, California, United States
Introduction: MM often becomes refractory early in its course, emphasizing a need for novel therapies. BMS-986393, a potential first-in-class autologous chimeric antigen receptor (CAR) T cell therapy targeting G protein-coupled receptor, class C, group 5, member D (GPRC5D), was safe and efficacious in pts with heavily pretreated RRMM (median 5 prior regimens) in the phase 1 CC‑95266‑MM‑001 study (NCT04674813). At 150 × 106 CAR T cells, the overall response rate (ORR) was 91% (complete response rate [CRR] 48%; Bal et al, ASH 2023). Here we present initial results in pts with RRMM and 1–3 prior anti-MM regimens from CC-95266-MM-001.
Methods: Pts had 1–3 prior anti-MM regimens including proteasome inhibitor and immunomodulatory agents; prior anti-CD38 therapy was not required. After screening and leukapheresis, pts received lymphodepleting chemotherapy followed by a single infusion of BMS‑986393 150 × 106 CAR T cells. The primary objective was safety. Secondary objectives included clinical activity per IMWG Uniform Response Criteria and pharmacokinetics (PK).
Results: As of Mar 18, 2024, 31 pts had received BMS-986393. Median age was 62 y (range 31–78); 19% were Black or African American; 29% had extramedullary disease. High-risk cytogenetics (del[17p], t[4;14], and/or t[14;16]) were seen in 26%, and 65% had 1q21 gain/amp. Pts had received a median of 2 prior regimens; 29% had 3 prior regimens. Around half (52%) had prior stem cell transplantation; 71% had received anti-CD38 therapy; 90% were lenalidomide-refractory; 55% were triple-class refractory; 90% had MM refractory to the last regimen, and 3% had prior B-cell maturation antigen (BCMA)-targeted therapy.
Median follow-up was 4.9 mo. Treatment-emergent adverse events (TEAEs) occurred in 97%, 81% experienced a grade (G) 3/4 TEAE; there were no deaths. Treatment-related AEs (TRAEs) occurred in 94%; 42% had a G3/4 TRAE. Cytokine release syndrome was reported in 81% (all G1/2; all resolved); no pts had macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 10% (all resolved; all G1/2), 10% had a non-ICANS neurotoxicity TRAE (n = 2 dizziness, n = 1 ataxia; all G1/2), and 48% had an on-target/off-tumor TRAE of the mouth, nails, or skin (all G1/2).
Of 24 pts evaluable for efficacy, 23 achieved a response for an ORR of 96%. The CRR was 42%. Of 23 responses, 87% were ongoing.
PK analyses showed fast and robust cellular expansion. Pharmacodynamic longitudinal assessment of soluble BCMA indicated BMS-986393 led to deep tumor clearance post-infusion.
Conclusions: Initial results suggest that a single infusion of BMS-986393 is safe and has promising preliminary efficacy in pts with RRMM and 1–3 prior regimens. While follow-up is limited, the safety profile of BMS-986393 at 150 x 106 CAR T cells was favorable with no new safety signals. High response rates were achieved. These data support BMS-986393 as a potential early-line treatment in RRMM. The trial is ongoing.
