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

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.

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.

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