OA – 30: Phase 1 Study Of Anitocabtagene Autoleucel For The Treatment Of Patients With Relapsed And/Or Refractory Multiple Myeloma: Results From At Least 1-year Follow-up In All Patients

Introduction: Anitocabtagene autoleucel (anito-cel, formerly CART-ddBCMA) is an autologous D-Domain BCMA-directed chimeric antigen receptor (CAR) T-cell therapy being studied in relapsed and/or refractory multiple myeloma (RRMM).

Methods: Details of study have been previously reported (Frigault et al Blood Adv 2023). Patients (pts) with RRMM who had received ≥3 prior lines of therapy received a single infusion of anito-cel following lymphodepletion chemotherapy. Two doses (DL1 & DL2, respectively) of 100 and 300 (±20%) × 10⁶ CAR+ cells were evaluated. The primary endpoints were incidence of adverse events and dose-limiting toxicities. Additional endpoints included quality & duration of clinical response assessed according to the IMWG Uniform Response Criteria for MM, evaluation of minimal residual disease (MRD), progression-free (PFS) & overall survival (OS).


Results: At a median follow-up 26.5 months (range: 14 – 44), 40 pts (median age 66 years, range: 44-76) were enrolled and 38 received anito-cel (32, DL1; 6, DL2). Two pts not dosed had cell product manufactured but were not eligible for infusion due to medical complications. Pts had a median of 4 (range: 3-16) prior lines of therapy. All infused pts (100%) were triple-refractory, 26 (68%) were penta-refractory, 34 (89%) were refractory to last-line of treatment; 9 (24%) had high tumor burden, 13 (34%) had extramedullary disease, & 11 (29%) had high-risk cytogenetics (Del 17p, t(14;16), t(4;14)). CRS occurred in 36/38 (95%) pts; 1 pt in DL2 had grade (Gr) 3 CRS & all other cases were Gr≤2. ICANS occurred in 7 pts (5, Gr≤2; 2, Gr3), with 1 Gr3 case in each DL. All cases of CRS & ICANS resolved with management and without sequalae. No delayed neurotoxicities were observed through the follow-up period. All 38 pts demonstrated investigator-assessed response per 2016 IMWG criteria (ORR, 100%) with 22 sCR & 7 CR (≥CR rate, 76%), 6 VGPR (≥VGPR rate, 92%), & 3 PR. Conversions to sCR occurred from 1 to >12 months. Of those evaluable for MRD testing to date (n=28), 25 (89%) were MRD-neg at 10^-5. Median duration of response, PFS, & OS were not reached; Kaplan-Meier estimated PFS rates for 6, 12, 18 & 24 months were 92%, 76%, 64%, and 56%, respectively. Durable responses in patients with high-risk features (EMD, BMPC ≥ 60%, or B2M ≥ 5.5mg/L), age >65 years, and high-risk cytogenetics were consistent with the overall study population. A dose of 115 ± 10 × 10⁶ CAR+ cells was recommended for the ongoing phase 2 study, iMMagine-1.


Conclusions: Adverse events with anito-cel, including CRS & ICANS, were manageable; no off-tumor tissue-targeted toxicity, delayed neurotoxicity nor Parkinsonian-like events were observed at time of data-cut. Efficacy analyses demonstrated 100% ORR, including 92% with VGPR or better & 76% with CR/sCR. Clinical responses were durable with an overall estimated 24-mo PFS rate of 56% with comparable responses seen in pts with ‘high-risk’ disease characteristics.