(OA-08) Three-Year Follow-Up of FUMANBA-1: a Phase 1b/ 2 Study of Fully Human Anti-BCMA CAR-T Equecabtagene Autoleucel in Patients with Relapsed/Refractory Multiple Myeloma

Equecabtagene Autoleucel (Eque-cel) is a fully human B-cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (RRMM). Eque-cel was approved in China to treat adult patients with RRMM who have received three or more lines of prior therapies, including at least one proteasome inhibitor and an immunomodulatory agent. FUMANBA-1, the phase 1b/2 study evaluating the safety and efficacy of Eque-cel, was conducted at 14 sites in China and here we report the updated trial results with a median follow-up of 36.0 months.

Methods: RRMM patients who had received at least three prior lines of therapy and with progressive disease after the last line of therapy were enrolled. Patients with extramedullary disease (EMD) or prior exposure to BCMA-targeted CAR-T therapy were included. Following lymphodepletion with cyclophosphamide (500 mg/m²) and fludarabine (30 mg/m²) for three consecutive days, a single infusion of CAR-T cells (1×10⁶ cells/kg) was administered. Efficacy and safety outcomes were assessed with a data cutoff of December 31, 2024.

Results:

A total of 109 patients received Eque-cel. The median lines of prior therapy was 4 (range 3-23).70.6% of patients had high-risk cytogenetic abnormalities (defined as at least one of t(4;14), t(14;16), t(14;20), Del 17p, and Gain 1q is positive), including 29.4% with two high-risk cytogenetic abnormalities. 12.8% had EMD and 11% had received prior BCMA CAR-T therapy.

Among 107 evaluable patients, the overall response rate (ORR) was 96.3%, including a complete or stringent complete response (CR/sCR) in 83.2%. In CAR-T–naïve patients, ORR and CR/sCR rates were 98.9% and 88.4%, respectively. Among 109 patients who received Eque-cel, the median progression-free survival (PFS) was 30.5 months (95% CI: 24.1–42.2), extending to 35.9 months (95% CI: 26.0–47.7) in CAR-T–naïve patients. Median overall survival (OS) was not reached. Minimal residual disease (MRD) negativity was achieved in 95.3% (102/107) of evaluable patients, including all those with ≥CR. The median duration of MRD negativity was 36.5 months (95% CI: 25.6–NE).

Cytokine release syndrome (CRS) occurred in 93.6% (102/109) of patients, with only one case ≥ grade 3. The median time to onset was 6 days (range: 1–13), and the median duration was 5 days (range: 2–30). Immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in two patients (grade 1–2). No late-onset neurotoxicity or secondary malignancies were observed. CAR transgene persistence was observed in 52% (39/75) of patients at 12 months and 37.5% (21/56) at 24 months. Anti-CAR antibodies were detected in 24.8% of patients.

Conclusions: At a median follow-up of 36.0 months, Eque-cel therapy demonstrated deep, durable responses and sustained MRD negativity in heavily pretreated RRMM patients, including those with high-risk features. The long-term safety profile remained manageable, with no new safety signals identified.