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761 Efficacy Outcomes and Characteristics of Patients with Multiple Myeloma (MM) Who Achieved Sustained Minimal Residual Disease Negativity after Treatment with Equecabtagene Autoleucel (Eque-cel, CT103A) in Fumanba-1

Program: Oral and Poster Abstracts
Type: Oral
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Immunological Effects of Sustained Responses in Multiple Myeloma
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Monday, December 11, 2023: 11:30 AM

Chunrui Li1, Lu-Gui Qiu2, Di Wang1*, Yongping Song, MD3*, He Huang4*, Jianyong Li, MD5, Bing Chen6, Jing Liu7*, Yujun Dong8*, Kai Hu9*, Peng Liu10*, Xi Zhang, PhD11, Jianqing Mi12*, Zhenyu Li13*, Kaiyang Ding14*, Shiyue Zhang15*, Guang Hu15* and Wen Wang15*

1Institute of Hematolog; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Tianjin, CHN
3Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
4Bone Marrow Transplantation Center, Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, Hangzhou, China
5Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
6Department of Hematology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
7Department of Hematology, Third Xiangya Hospital of Central South University, Changsha, China
8Department of Hematology, Peking University First Hospital, Beijing, CHN
9Department of Adult Lymphoma, Beijing Boren Hospital, Beijing, China
10Department of Hematology, Zhongshan Hospital, Fudan University,Shanghai,China, Shanghai, CHN
11Army medical University affiliated Xinqiao Hospital, Chongqing, China
12State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, CHN
13Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
14Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Anhui, China
15Nanjing IASO Biotherapeutics Ltd, Nanjing, China

Background: Equecabtagene autoleucel (eque-cel, CT103A), which is designed with a fully human BCMA-specific CAR structure, was recently granted NMPA approval for the treatment of adult patients (pts) with relapsed/refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOT). The pivotal phase 2 FUMANBA-1 study (NCT05066646) demonstrated deep and durable responses with eque-cel in heavily pretreated patients with RRMM. Recent studies have demonstrated the utility of minimal residual disease (MRD) as a prognostic biomarker for long-term outcomes of RRMM, wherein achievement of sustained MRD-negative status was associated with an improvement in PFS of pts treated by eque-cel in FUMANBA-1 study. We sought to characterize the baseline and disease characteristics of pts with sustained MRD negativity (pts who continued to remain MRD negative ≥6 mo and ≥12 mo).

Methods: FUMANBA-1 study enrolled RRMM pts who received ≥ 3 lines of prior therapies containing at least a proteasome inhibitor and an immunomodulatory agent and were refractory to their last line of treatment. All pts received a single infusion of eque-cel at the dose of 1.0 x 106 CAR-T cells/Kg. Pts who had progressed on previous BCMA CAR-T cell therapy were not included in this analysis. The primary endpoint was ORR. Additional endpoints included ≥CR rate (key secondary), DOR, PFS, and safety. ORR and CR were assessed per IMWG criteria; DOR and PFS were analyzed via Kaplan-Meier methods. MRD negativity was a secondary objective and was assessed on bone marrow samples at baseline; day 14, 28; and 2, 3, 6, 9, 12, 15, 18, 21 and 24 mo using EuroFlow next-generation flow, regardless of disease status. Evaluable samples passed calibration and quality control and included sufficient cells for evaluation at 10-5 testing threshold. Characteristics were analyzed in pts who had MRD negativity <6 mo, or sustained ≥6 mo and ≥12 mo. Pts who did not achieve MRD negativity at any time point were considered to be MRD positive.

Results: Of the 88 pts who achieved MRD negativity in FUMANBA-1, 74 had at least 6 mo follow up without progression after initial MRD-negativity and 43 had at least 12 mo follow up without progression after initial MRD-negativity. MRD negativity was sustained for ≥6 mo in 78.4% (58 of 74 with at least 6 mo follow-up without progression after initial MRD-negativity) and ≥12 mo in 74.4% (32 of 43 with at least 12 mo follow-up without progression after initial MRD-negativity; 7 pts evaluable for sustained MRD at ≥6 mo but not ≥12 mo had PD). Pts with sustained MRD negativity (≥6 mo, and ≥12 mo) had longer progression free survival (PFS; Figure 1A) compared with pts who did not (MRD negative <6 mo). Key pt and disease characteristics in these different groups (Figure 1B), and potential associations with sustained MRD negativity were analyzed descriptively. Baseline R-ISS disease stage III was more common in pts with MRD sustained for ≥6 mo (8.6%) and ≥12 mo (9.4%) compared with pts who had MRD negativity <6 mo (3.3%). Baseline high tumor burden diseases were less common in pts with MRD sustained for ≥6 mo (70.7%) and ≥12 mo (65.6%) compared with pts who had MRD negativity <6 mo (90%). Triple-class exposure was also less common in pts with MRD sustained for ≥6 mo (12.1%) and ≥12 mo (12.5%) compared with pts who had MRD negativity <6 mo (30%). Pts with sustained MRD negativity had trends toward shorter median time since diagnosis (38.6 mo and 40.2 mo for pts with MRD negativity sustained ≥6 and ≥12 mo, respectively versus 43.5 mo for those with MRD negativity <6 mo). Other baseline characteristics, including presence of high-risk cytogenetics, ECOG performance status, extramedullary disease and number of prior LOT did not differ across MRD subgroups, and were similar to the overall FUMANBA-1 population.

Conclusions: Based on our descriptive analysis, pts receiving eque-cel achieved MRD negativity irrespective of their high-risk cytogenetics, extramedullary disease, number of prior LOT and performance status. Presence of high tumor burden at baseline, and prior triple-class exposure might be factors that impact achievement of sustained MRD negativity. These data suggest that while eque-cel is effective for a broad range of pts, specific pt and disease characteristics may be associated with sustained MRD negativity and better long-term outcomes. Sustained MRD negativity might be a promising prognostic indicator for RRMM pts treated by eque-cel.

Disclosures: Zhang: Nanjing IASO Biotherapeutics Ltd: Current Employment. Hu: Nanjing IASO Biotherapeutics Ltd: Current Employment. Wang: Nanjing IASO Biotherapeutics Ltd: Current Employment.

*signifies non-member of ASH