Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2)

Abstract

Background: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years.

Methods: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 10⁶ cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy.

Results: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer.

Conclusions: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

Keywords: B cell maturation antigen; Chimeric antigen receptor therapy; Efficacy; Multiple myeloma; Safety.

Fig. 1

A Best response in all patients. B Duration of response in patients with a response (≥ PR). CR complete response, MRD minimal residual disease, NE not evaluable, ORR overall response rate, PD progressive disease, PR partial response, SD stable disease, VGPR very good partial response. ^aORR includes patients with ≥ PR. ^b8-color flow cytometry with cell count up to 500,000 cells. ^c1 patient died of pulmonary embolism/acute coronary syndrome prior to evaluation, 1 patient died on day 13 due to CRS and TLS, and 1 patient received chemotherapy prior to first assessment and was censored

Fig. 2

A Progression-free survival and B overall survival by CR. CI confidence interval, CR complete response, NE not evaluable, OS overall survival, PFS progression-free survival

Fig. 3

Overall survival (left) and progression-free survival (right) by A sBCMA decline, B transgene persistence, and C ADA. 280 days is the median T_last value for the patient population. ADA antidrug antibody, BL baseline, sBCMA soluble B cell maturation antigen, T_last last time point of detectable transgene

Fig. 4

A Overall survival and B progression-free survival by hypogammaglobulinemia resolving status in patients with PR or better. Ig Immunoglobulin, PR partial response