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
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