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3357 Phase 2, Open-Label Study of Ciltacabtagene Autoleucel, an Anti-BCMA CAR-T Cell Therapy, in Chinese Patients with Relapsed/Refractory Multiple Myeloma (CARTIFAN-1): 26-Month Median Follow-up

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Jian-Qing Mi1*, Wanhong Zhao2*, Hongmei Jing3*, Weijun Fu4, Jianda Hu5, Lijuan Chen6*, Yiwen Zhang7*, Dan Yao8*, Hui Li8*, Jordan M Schecter9, Fan Yang8*, Huabin Sun9*, Sen Hong Zhuang8*, Da Xu7*, Tracy Luo7*, Xiaohu Fan10*, Ting Niu11, Jie Jin12 and Sai-Juan Chen1

1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, ShaanXi, Shanxi, China
3Peking University Third Hospital, Beijing, China
4Shanghai Changzheng Hospital and Department of Hematology, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
5Fujian Medical University Union Hospital, Fuzhou, Fujian, China
6Jiangsu Province Hospital, Nanjing, Jiangsu, China
7Legend Biotech China, Nanjing, Jiangsu, China
8Janssen China Research & Development, Shanghai, China
9Janssen Research & Development, Raritan, NJ
10Xi’an Jiaotong University Institute of Gene and Cell Therapy, Xi’an, ShaanXi, China
11West China Hospital of Sichuan University, Chengdu, China
12First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China

Introduction: Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor (CAR)-T cell therapy with 2 B-cell maturation antigen (BCMA)–targeting single-domain antibodies approved for the treatment of relapsed/refractory multiple myeloma (RRMM) in the US and EU. In China, MM incidence and mortality rates have increased or remained stable in recent years (Liu J et al, JHO, 2019), and more effective RRMM therapies are needed. Recently approved therapies for patients in China with RRMM after ≥2 prior lines of therapy (LOT) have only modest efficacy (overall response rate [ORR], 31–36%; median progression-free survival [PFS], 4–6 months) (San Miguel J et al, Lancet Oncol, 2013; Du J et al, Int J Hematol, 2021). In the CARTIFAN-1 study (NCT03758417), a single infusion of cilta-cel led to early, deep, and durable responses in heavily pretreated Chinese patients with RRMM (Mi J et al, JCO, 2022, in press). Initial results at a median follow-up of 18 months showed an ORR of 85.4%, with 75% of patients achieving a stringent complete response (sCR); median duration of response (DOR), PFS, and overall survival (OS) were not reached (NR). Here, we report updated efficacy and safety data from CARTIFAN-1 with a longer median follow-up of 26.4 months.

Methods: CARTIFAN-1 is an ongoing, phase 2, open-label study conducted across 8 sites in China. Adult patients with MM were enrolled if they had received ≥3 prior LOT, including a proteasome inhibitor and an immunomodulatory drug. Patients received a single infusion of cilta-cel at a target dose of 0.75×106 CAR-positive viable T cells/kg. The primary endpoint was ORR, the proportion of patients achieving a partial response (PR) or better, assessed by a computerized algorithm per International Myeloma Working Group criteria. Secondary endpoints included rates of sCR, CR, and very good PR (VGPR); minimal residual disease (MRD) negativity measured using flow cytometry (10-5 threshold); and DOR, PFS, OS, and incidence and severity of adverse events (AEs).

Results: As of the April 19, 2022 clinical cutoff, corresponding to a median follow-up of 26.4 months (minimum 18 months), the 48 patients (median age, 61 years [range, 30–72]) who had received cilta-cel had a median of 4 prior LOT (range, 3–9), 31% were triple-class exposed, 19% were triple-class refractory, and 98% were refractory to their last LOT. Since the last data cut (July 2021), the ORR remained at 85.4% (95% CI, 72.2–93.9), but responses deepened, with 79.2% of patients (95% CI, 65.0–89.5) achieving sCR. Median DOR was NR. Responses adjudicated by an Independent Review Committee yielded similar results (Figure 1A). Of the 41 evaluable patients, 40 (97.6%; 95% CI, 87.1–99.9) were MRD negative. Median PFS and OS were NR; 24-month PFS and OS rates were 52.6% (95% CI, 36.5–66.4) and 74.2% (95% CI, 58.8–84.5), respectively. Patients who achieved sustained MRD negativity for ≥12 months had more favorable PFS than the overall population (Figure 1B). All patients experienced ≥1 grade 3/4 treatment-emergent AEs (TEAEs). The most common TEAEs were hematologic. Grade 3/4 cytopenias included neutropenia (97.9%), lymphopenia (91.7%), thrombocytopenia (54.2%), and anemia (52.1%). The overall incidence of cytokine release syndrome (97.9%), hemophagocytic lymphohistiocytosis (6.3%), CAR-T cell neurotoxicity (4.2%), and infection (85.4%) remained consistent since the previous data cut. There were no cases of parkinsonism/movement and neurocognitive TEAEs. A total of 12 deaths post cilta-cel infusion (8 considered treatment-related) were reported. At data cutoff, 36 cilta-cel–treated patients remained on study; 16 patients have remained disease-free for ≥24 months and 1 patient for ≥36 months.

Conclusions: At a longer median follow-up of 26.4 months, responses to cilta-cel deepened over time and the risk-benefit profile remains favorable. These results in Chinese patients with RRMM, for whom there is an urgent, unmet clinical need, are consistent with those observed in the CARTITUDE-1 study. It will be important to consider risk mitigation strategies and prompt supportive care for patients treated with CAR-T therapy in China in current and future clinical studies and practice.

Figure 1. (A) Table of outcomes by IRC assessment vs computerized algorithm (B) Kaplan-Meier curves of progression-free survival based on computerized algorithm.

Disclosures: Li: Janssen China Research & Development: Current Employment. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Yang: Janssen Research and Development: Current Employment. Sun: Janssen Pharmaceutical Company: Current Employment, Current equity holder in publicly-traded company. Zhuang: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Luo: Legend Biotech: Current Employment. Fan: Legend Biotech: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Jin: The Second Affiliated Hospital of Xi'an Jiaotong University: Consultancy.

OffLabel Disclosure: Cilta-cel is a CAR-T therapy approved for patients with relapsed/refractory multiple myeloma after 4 or more lines of therapy

*signifies non-member of ASH