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4761 Impact of CAR T-Cell Persistence on Clinical Outcomes in Relapsed/Refractory Multiple Myeloma: Insights from the Phase 2 Fumanba-1 Study

Program: Oral and Poster Abstracts
Session: 655. Multiple Myeloma: Cellular Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Treatment Considerations, Biological therapies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Chunrui Li, MD, PhD1, Dehui Zou2*, Di Wang1*, Baijun Fang3*, He Huang4*, Jianyong Li, MD5, Bing Chen6, Jing Liu, PhD7*, Xi Zhang, PhD8, Yujun Dong9*, Kai Hu, MD10, Peng Liu, MD11, Jianqing Mi12, Kaiyang Ding13*, Zhenyu Li14*, Qie Dong15*, Fuyuan Zhang15*, Guang Hu, PhD15 and Lu-Gui Qiu2

1Institute of Hematology;Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
3Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
4The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
5Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
6Department of Hematology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
7Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China
8Medical Center of Hematology, Xinqiao Hospital of Army Medical University, State Key Laboratory of Trauma and Chemical Poisoning, Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, China
9Department of Hematology, Peking University First Hospital, Beijing, China
10Beijing GoBroad Boren Hospital, Beijing, China
11Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China
12State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
13Department of Hematology, The First Affiliated Hospital of USTC, Hefei, CHN
14The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
15Nanjing IASO Biotechnology Co., Ltd., Nanjing, China

Background: The persistence of CAR T cells is a critical factor in their therapeutic efficacy, particularly in the treatment of hematologic malignancies such as acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and large B-cell lymphoma (LBCL). Notably, in multiple myeloma (MM) therapies targeting B-cell maturation antigen (BCMA), prolonged CAR T-cell persistence has been linked to better clinical outcomes. In the FUMANBA-1 study, we previously confirmed a positive correlation between Equecabtagene Autoleucel (Eque-cel) persistence and the maintenance of MRD negativity, which was reported at the 2023 ASH conference (Wang D et al. 2023 ASH oral 4584).

Objective: This study aims to analyze the relationship between CAR T-cell persistence and progression-free survival (PFS) as well as time to progression (TTP). Additionally, the study examines how the baseline level of soluble B-cell maturation antigen (sBCMA) influences these outcomes.

Methods: A retrospective analysis was performed to analyze the population receiving Eque-cel treatment in the FUMANBA-1 study. CAR T-cell persistence was monitored via digital droplet polymerase chain reaction (ddPCR). The sBCMA levels were measured using enzyme-linked immunosorbent assay (ELISA). Patients were categorized based on the efficacy to target ratio (VCN duration/baseline sBCMA), with further analysis on PFS and TTP differences between the groups. Univariate and multivariate analyses were conducted to identify factors influencing CAR T-cell persistence.

Results: During a median follow-up of 24.67 months, 107 patients in 14 centers were treated with Eque-cel. The median efficacy-to-target ratio, measured by the vector copy number (VCN) duration to baseline soluble B-cell maturation antigen (sBCMA), was 1.05 (Days*mL/ng). Patients were categorized into two groups: a high efficacy-to-target ratio group and a low ratio group . Those with a lower ratio had a significantly higher risk of disease progression, with a hazard ratio (HR) for PFS of 2.3 (95% CI: 1.27–4.14, p = 0.0045) and for TTP of 3.07 (95% CI: 1.51–6.24, p = 0.0011), both indicating a strong correlation between the efficacy-to-target ratio and disease progression risk.

At the data cutoff, the ongoing remission group showed a longer median VCN duration than those with progression or relapse (12.52 vs. 9.03 months, p = 0.71), though this was not statistically significant. Among baseline characteristics, including ECOG score, R-ISS and ISS disease stages, tumor BCMA expression, tumor burden, baseline sBCMA level, previous autologous stem cell transplantation (ASCT), triple-class exposure, bridging therapy, prior CAR-T treatment, and lymphodepleting conditioning, only previous ASCT (n = 30) was significantly associated with Eque-cel persistence (HR = 0.35, p = 0.004).

Post-infusion, patients with anti-drug antibodies (ADA) had a significantly higher risk of shorter VCN duration (HR = 5.79, p < 0.0001). Notably, Cmax levels, whether above or below the median, did not significantly impact VCN duration (HR = 0.93, p = 0.78). Among the 107 patients, only 14 exhibited an aplastic neutrophil recovery phenotype, characterized by persistent neutrophil counts below 500/μl for 14 days or more. This phenotype did not significantly affect VCN duration compared to patients without this condition.

Conclusion: The efficacy-to-target ratio is a crucial determinant of clinical outcomes in patients treated with Eque-cel, underscoring the importance of CAR T-cell persistence. This ratio may serve as a biomarker for future treatment planning, highlighting the need for extended CAR T-cell persistence to achieve optimal disease control. While baseline characteristics like previous ASCT influence persistence, baseline sBCMA levels do not adversely affect the treatment efficacy of Eque-cel.

Disclosures: Dong: Nanjing IASO Biotechnology Co., Ltd: Current Employment. Zhang: Nanjing IASO Biotechnology Co., Ltd: Current Employment. Hu: Nanjing IASO Biotherapeutics Ltd: Current Employment.

*signifies non-member of ASH