Encouraging Efficacy and Safety Profile Demonstrated by Anito-Cel in R/R Multiple Myeloma

Binod Dhakal, MD, MS

Findings from a phase 1 (NCT04155749) trial evaluating the BCMA-directed chimeric antigen receptor (CAR) T-cell therapy, anitocabtagene autoleucel (anito-cel; CART-ddBCMA), demonstrated impressive and durable efficacy rates in patients with relapsed/refractory multiple myeloma. The therapy also elicited a manageable safety profile according to a presentation of the data during the 21st International Myeloma Society Annual Meeting.

Overall, patients demonstrated a response of 100% and a complete remission and a stringent complete remission (CR/sCR) rate of 76%. At a median follow-up of 26.5 months, investigators reported that median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) had not been reached at 2 years.

“It seems likely that the median for the entire difficult-to-treat patient population will be greater than 2 years,” said investigator Binod Dhakal, MD, MS, associate professor of medicine, Medical College of Wisconsin, Division of Hematology, in Milwaukee.

A total of 92% of patients (N = 38) achieved a CR/sCR and very good partial response rate. “Surprising CR/sCR rates were reported across patient subgroups, including patients with extramedullary disease [EMD; 85%; n =13], high-risk cytogenetics [82%; n = 11], high-risk cytogenetics with 1q gain [77%; n = 26], and patients over 65 years of age [85%; n = 20],” Dhakal continued.

CAR T-cell therapy in multiple myeloma: © Kasloom - stock.adobe.com

At the data cut-off of October 15, 2023, 89% (n = 25/28) of evaluable patients were minimal residual disease–negative at a minimum of 10-5 sensitivity.

In general, patients with EMD have a poor prognosis because of a shorter duration of response and overall survival. “I think the most impressive finding of this study, however, is that at a follow-up of 33 months, the median PFS was not reached in the EMD group,” Dhakal said.

In patients with EMD (n = 13), the 24-month PFS estimate rate was 57.5% (95% CI, 25.7%-79.9%) and the 18-month PFS estimate rate was 67.1% (95% CI, 34.2%-86.2%), investigators reported. “Follow-up in the non-EMD group was a little shorter at 25 months and is likely to evolve further,” Dhakal continued.

Overall, 6-month, 12-month, 18-month, and 24-month PFS rates were 92.1% (95% CI, 77.5%-97.4%), 75.9% (95% CI, 58.7-86.6%), 63.7% (95% CI, 45.7%-77.2%), and 56.0% (95% CI,37.3%-71.1%), respectively. Dhakal noted that the median was not reached in the overall population, as well as in patient subgroups.

“Some of the highest PFS rates at 24 months were reported in patients with high-risk features such as EMD,” Dhakal said.

Safety Profile

Turning to safety, Dhakal reported no cases of delayed neurotoxicity, no cases of Guillain-Barré syndrome, no cranial nerve palsies, and no Parkinsonian-like syndromes for the entire population through the follow-up period. There was 1 grade 5 adverse event (AE) post study, which was an unrelated cardiac arrest attributed to a non-study drug overdose.

The most common grade 3/4 hematologic AEs (n = 38) that were not attributable to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome were decreased neutrophil counts (81.6%), anemia (57.9%), and thrombocytopenia (42.1%). Among non-hematologic AEs, the most common were hypertension (7.9%), an increase in aspartate aminotransferase levels (5.3%), and cellulitis (5.3%).

Anito-cel is undergoing evaluation in the pivotal phase 2 iMMAgine-1 trial (NCT05396885) and the iMMagine-3 trial (NCT06413498), a global phase 3 trial comparing anito-cel to standard of care in patients with relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug (IMiD).

Trial Background

The phase 1 first-in-human trial evaluated patients with relapsed/refractory disease who received prior IMiD, proteasome inhibitor, and CD38-targeted therapy. Eligible patients had received 3 or more lines of therapy or were triple refractory.

There were 2 dose levels evaluated, with 6 patients in each dose escalation cohort. Based on the early data, the decision was made to expand dose level 1 (DL 1).

A total of 40 patients were enrolled and underwent leukapheresis; 1 patient discontinued due to infection. Thirty-nine patients received lymphodepletion and 1 patient discontinued due to hypoxia/heart failure, resulting in 32 patients who received DL 1 (100 × 106 CAR+ cells) and 6 patients who received DL 2 (300 ×106 CAR+ cells).

The overall median age was 66 years (range, 44-75). For patients in DL 1, the median age was 66 years (range, 44-76) and for DL 2, the median age was 60 years (range 52-65). The majority of patients were male (61%) and 32% of patients were ECOG performance status 0 and 68% were ECOG performance status 1.

Sixty-three percent of patients had at least 1 high-risk prognostic feature, which was defined as bone marrow plasma cells greater than 60%, ISS stage 3 disease, and EMD. EMD was present in 34% of patients overall.

High-risk cytogenetics that included 1q was seen in 64% of patients but if 1q was excluded, only 29% of patients had it. All patients were triple class refractory and 68% were penta-refractory.

REFERENCE:

Frigault M, Rosenblatt J, Dhakal B, et al. Phase 1 study of anito-cel (CART-ddBCMA) for the treatment of patients with relapsed and/or refractory multiple myeloma: results from at least 1-year follow-up in all patients. Presented at: 21st International Myeloma Society Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil. Abstract OA-30.