Background:

Equecabtagene autoleucel (eque-cel), a fully human BCMA-targeted CAR-T therapy, has exhibited unprecedented efficacy in relapsed/refractory multiple myeloma (RRMM) patients with ≥3 prior lines of therapy (LOT), achieving 96% overall response rates (ORR) in clinical trials. Despite its 2023 approval in China, critical knowledge gaps persist regarding its real-world applicability across heterogeneous patient populations.

Method:

This is a single-center retrospective study that evaluates the efficacy, safety, and durability of eque-cel in Chinese RRMM patients. The prior lines of treatment (LOT), baseline characteristics before eque-cel infusion, as well as the safety and efficacy of eque-cel were recorded. Categorical variables were analyzed using Fisher's exact test. Survival outcomes including progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier methodology and significance testing was conducted using the Log-rank method. We also performed Cox regression analyses for PFS as univariate analyses.

Results:

From June 2023 to February 2025, totally 45 patients were enrolled, 22 (48.9%) were male, with a median age of 61 years (range, 30-75 years). High-risk cytogenetic abnormalities included G(1q21) in 46.7% (21/45), t(4;14) in 15.6% (7/45), and TP53/del(17p) mutation in 33.3% (15/45). Fifteen patients (33%) harbors at least two high-risk cytogenetic abnormalities. The median number of prior LOT was 2 (range, 1-7), with 46.7% (21/45) having received ≥3 lines. The triple-class exposed rate was 68.9% (31/45), and the autologous stem cell transplantation (ASCT) rate was 37.8% (17/45). All patients received FC lymphodepleting regimen and underwent infusion of 1×10⁶/kg CAR-T cells. The median leukapheresis to infusion interval was 57 days (range, 22-203 days). Individualized bridging therapies were used in 100% of patients.

Adverse events were manageable. Cytokine release syndrome (CRS) occurred in 84.4% (38/45) of patients, with grade 3 CRS in 4.4% (2/45) who had received 5 and 7 prior LOT, respectively; immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 6.7% (3/45), comprising two grade 1 events and one grade 3 event. The patient with grade 3 ICANS had received 5 prior LOT. Hematologic toxicities were common, with grade 3-4 neutropenia, anemia, and thrombocytopenia occurring in 60.0% (27/45), 31.1% (14/45), and 24.4% (11/45) of patients, respectively. Non-hematologic toxicities such as nausea (11.1%), diarrhea (20.0%), and headache (4.4%) were less frequent. Infections occurred in 51.1% (23/45) of patients, with grade 3-4 infections in 26.7% (12/45).

Before eque-cel infusion, 16 attained complete response (CR), 4 attained VGPR, 12 patients remained with a high M-protein load (≥10 g/L), 2 patients PD, while all the rest were SD. Median follow up 196 days (range, 18-596 days), the overall response rate (ORR) was 95.6%, with 82.2% achieving ≥CR. Furthermore, 93.3% of patients achieved minimal residual disease (MRD) negativity. The median time to response was 28 days (range, 14-85 days). The median time to best response was 60 days (range, 14-231 days). The median PFS and OS were both not reached. For all patients, 1-2 LOT and ≥3 LOT, the 12-month PFS rate were 74.9%, 91.5% and 63.1%, respectively, and the 12-month OS rate were 91.0%, 100% and 82.5%, respectively. Two patients died from infection at 1 month, the other one died at 3 month with unknown reason. Cell kinetic analysis confirmed the presence of CAR-positive T cells in all patients, with median time to peak was 10 days, and the median peak concentration was 423.32 cells/μL. Univariate analysis indicated that 1q21 amplification was significantly negatively correlated with ORR (100% vs 61.9%, p=0.001). Heavily pretreated patients (≥3 lines) and triple-refractory disease showed a trend toward inferior ORR, while patients with t(11;14) translocation showed a trend toward longer PFS (the 12-month PFS rate 100% vs 68.3%, p=0.056).

Conclusion:

This is the first report on the efficacy and safety of eque-cel in real-world patients with RRMM, which confirmed that eque-cel provided early and deep responses in heavily pretreated RRMM patients, with a manageable safety profile. Preliminary findings from the exploration in early-line RRMM patients also support further investigation in this population.

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2025
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