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.

Conflict of interest statement

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki and was approved by the institutional independent ethics committee (reference number: 2016002) of The Second Affiliated Hospital of Xi’an Jiaotong University. All patients provided written informed consent.

Consent for publication

Consent from patients whose data are included in this article has been obtained in writing.

Competing interests

Q-CZ and X-HF are employees of Nanjing Legend Biotech Co. All other authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

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