BCMA-Targeting CAR T-Cell Therapy Effective in R/R Myeloma?

Article

A phase I study examines the use of LCAR-B38M, a CAR T-cell therapy directed against BCMA, in patients with relapsed/refractory multiple myeloma.

A phase I study out of China has provided additional evidence that chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) leads to deep and durable responses in some patients with relapsed/refractory multiple myeloma.

BCMA is widely expressed on the surface of myeloma cells, but has low expression on normal cells, making it a good target for treatment. Two previous phase I studies – CAR-BCMA and bb-2121 –have tested CAR T cells targeting BCMA in heavily pretreated patients with myeloma and shown promising results with overall response rates of 80% or greater.

Wan-Hong Zhao, of the Second Affiliated Hospital of Xi’an Jiaotong University, China, and colleagues tested LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against two BCMA epitopes.

The ongoing study included 57 patients with relapsed or refractory disease who had received infusion with LCAR-B38M CAR T cells at data cutoff. The median age of patients was 54 years, and the median number of prior lines of therapy was three.

Median time to response was 1 month. The overall response rate was 88%. More than half (68%) of patients had a complete response with an additional 5% achieving very good partial response and 14% achieving partial response. Additionally, 63% of patients were negative for minimal residual disease (MRD).

Twenty percent of patients who initially achieved partial response or better subsequently progressed by data cutoff. With a median follow-up of 8 months, median progression-free survival was 15 months. Median overall survival has not yet been reached.

About half of patients (49%) had less than 40% BCMA expression. Level of BCMA expression did not appear to correlate with clinical response to treatment. The overall response rate was 92% in patients with less than 40% BCMA expression and 82% in patients with 40% or more.

All patients experienced at least one adverse event and grade 3 or worse events were reported in 65% of patients. Grade 3 or worse leukopenia occurred in about one-third of patients and about one in five experienced thrombocytopenia and increased aspartate aminotransferase.

Ninety percent of patients experience cytokine release syndrome including 7% who had grade 3 or worse cases. Median time to onset of CRS was 9 days. All cases were resolved with a mediation duration of 9 days, except for one patient who had grade 5 adverse events. Neurotoxicity occurred in one patient, with events resolved within one day.

“This ongoing first-in-human study has provided initial proof-of-concept that dual epitope-binding LCAR-B38M CAR T cells may be a highly effective therapy for patients with relapsed or refractory multiple myeloma,” the researchers wrote. “Further clinical evaluation of this promising and potentially transformational treatment approach is underway, with an ongoing phase 1b/2 study in the US.”

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