DdBCMA-Targeted CAR-T Therapy Continues to Show Promise in Multiple Myeloma


Among the 38 patients now dosed and evaluable, the ORR remains at 100%.

CART-ddBCMA, an investigational autologous chimeric antigen receptor (CAR) T-cell therapy which uses a novel synthetic binding domain referred to as a D-Domain to target B-cell maturation antigen (BCMA), has continued to demonstrate clinical activity and a manageable safety profile in a phase 1 study (NCT04155749) for patients with relapsed/refractory (r/r) multiple myeloma (MM), according to updated data presented in a poster at the 64th Annual American Society of Hematology (ASH) Meeting, held December 10-13, 2022, in New Orleans, Louisiana.1

Among the 38 patients evaluable (minimum follow-up, 1 month), the overall response rate measured by International Myeloma Working Group (IMWG) criteria was 100% and the complete response (CR) or stringent CR (sCR) rate was 71%, with a very good partial response (VGPR) rate of 18%.1,2 Among patients with at least 12 months of follow-up (n=25), the CR/sCR rate was 80% and VGPR was 12%; among patients with at least 18 months of follow-up (n=16), the CR/sCR rate was 81% and the VGPR rate was 6%. The progression-free survival rate was 91.8% at 6 months, 72.7% at 12 months, and 64.6% at 18 months. Of the 27 patients evaluable for minimal residual disease (MRD), 89% achieved negativity.

In terms of safety, there were no tissue-targeted toxicities reported and no patients showed delayed neurotoxicity or parkinsonian-like symptoms. Among the 32 patients treated at the lower dose level (100x106 CAR+ cells), a single grade 3 case of immune effector cell-associated neurotoxicity syndrome (ICANS) occurred and there were no cases of grade 3 cytokine release syndrome (CRS).

CART-ddBCMA continues to demonstrate deep responses,” Matthew J. Frigault, MD, study investigator and assistant director of the Cellular Therapy Service at Mass General Cancer Center and instructor at Harvard Medical School, said in a press release regarding the data.2 “It is encouraging to see these clinical results with an autologous cell therapy, particularly in a population with high-risk features. Accessibility to treat multiple myeloma patients with CAR-T therapy remains an issue."

As of the October 31, 2022, data cut-off, 38 participants with a median age of 66 years (range: 44-76) had received CART-ddBCMA.1,2 The group included 23 male patients and 15 female patients. Participants had an Eastern Cooperative Oncology Group score of either 0 (n=12) or 1 (n=26). The majority of the included patients (58%) had high risk prognostic features and had received a median of 4 prior lines of therapy (range 3-16). All of the patients were at least triple-refractory and 68% were penta-refractory.

Among the 6 patients treated at the higher dose level (300x106 CAR+ cells), there were 5 cases of grade 1 or grade 2 CRS, and 1 case of grade 3 CRS. A single grade 3 case of ICANS occurred in this group, but no cases of grade 1 or grade 2 ICANS. In the lower dose group, there were 30 cases of grade 1 or grade 2 CRS, and 5 cases of grade 1 or grade 2 ICANS.

A phase 2 clinical trial (NCT05396885; iMMagine-1) for CART-ddBCMA has already begun recruiting participants, and the first patient has been dosed. Participants in the trial will receive the recommended phase 2 dose, 115±10x106 CAR T-cells, via intravenous infusion. The multicenter, open-label study will seek to enroll 110 patients with r/r MM with a primary end point of overall response rate.

For more coverage of ASH 2022, click here.

1. Frigault M, Rosenblatt JR, Dhakal, B, et al. Phase 1 Study of CART-Ddbcma for the Treatment of Subjects with Relapsed and /or Refractory Multiple Myeloma. Presented at: 2022 ASH Annual Meeting. December 10-13, 2022; New Orleans, LA. Abstract 33132.
2. Arcellx announces continued robust long-term responses from its CART-Ddbcma phase 1 expansion trial in patients with relapsed or refractory multiple myeloma and additional pipeline progress. News release. Arcellx, Inc. December 9, 2022. https://ir.arcellx.com/news/news-details/2022/Arcellx-Announces-Continued-Robust-Long-Term-Responses-from-its-CART-ddBCMA-Phase-1-Expansion-Trial-in-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma-and-Additional-Pipeline-Progress/default.aspx 
Related Videos
Subhash Tripathi, PhD, on Generating In Vivo CARs With A2-CAR-CISC EngTreg Cells
Luke Roberts, MBBS, PhD, on Challenges in Developing Gene Therapy for Heart Failure
Steve Kanner, PhD, the chief scientific officer of Caribou Biosciences
Lisa Nieland on Slowing Tumor Growth in Glioblastoma With Novel AAV Therapy
Manali Kamdar, MD, on Acclimating to Routine CAR T Practice in the Field
Leigh Ramos-Platt, MD, on Looking Forward to Gene Therapy’s Growth
Manali Kamdar, MD, on Evaluating Liso-Cel in Mantle Cell Lymphoma by Lines of Therapy, Prior BTKi
Subhash Tripathi, PhD, on Developing Safe, Specific Engineered Treg Cell Therapy
Mark Walters, MD
Sharif Tabebordbar, PhD, on Improving In Vivo Gene Editing for DMD
© 2024 MJH Life Sciences

All rights reserved.