A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma

Abstract

Background: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).

Methods: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m². LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10⁶ cells/kg [range, 0.07 to 2.1 × 10⁶]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.

Results: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.

Conclusions: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.

Trial registration: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

Keywords: BCMA; CAR T; Chimeric antigen receptor; Multiple myeloma; Refractory; Relapsed.

Fig. 1

Efficacy assessments of LCAR-B38M. a Individual patient response and duration of follow-up for patients who achieved at least a PR (n = 50). b One patient manifested extramedullary myeloma and wide subcutaneous metastasis. Examination on day 1, day 19, and day 84 after LCAR-B38M CAR T cell infusion showed regression of the subcutaneous metastases. c CT scans of a patient with an extramedullary lesion beside the thoracic vertebrae and severe pleural effusion at baseline and at week 3 and week 8 following LCAR-B38M CAR T cell infusion. It should be noted that the patient received thoracentesis intermittently before the CAR T treatment but did not receive thoracentesis or intrathoracic injection of drugs after treatment

Fig. 2

Progression-free survival and overall survival. a The Kaplan-Meier curve for progression-free survival for all treated patients. The median progression-free survival was 15 months (95% CI, 11 to not estimable). b The Kaplan-Meier curve for overall survival for all treated patients. The median overall survival was not reached. The dotted lines represent 95% confidence intervals