Chimeric antigen receptor (CAR) T-cell therapy with 2 different targets can produce durable responses for patients with relapsed or refractory multiple myeloma (MM), according to a phase 2 trial published in the Journal of Clinical Oncology

Patients who received CAR-T cells targeting B-cell maturation antigen (BCMA) and CD19 had an overall response rate of 92%, and the median duration of response was 20.3 months.  

This phase 2 trial enrolled 62 patients with relapsed or refractory MM. They all received anti-BCMA and anti-CD19 CAR-T cells. The patients’ median age at CAR T-cell infusion was 58 (range, 30-69) years, and the median time since diagnosis was 30 (range, 8-167) months. 


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Overall, 48% of patients had stage III disease, 24% had extramedullary disease, and 29% had high-risk cytogenetic abnormalities. The patients had received a median of 4 (range, 2-17) prior lines of therapy, and 27% had received an autologous stem cell transplant before CAR T-cell infusion.

At a median follow-up of 21.3 months, the overall response rate was 92%, and the median duration of response was 20.3 months. 

In all, 47% of patients achieved a complete response (CR) or stringent CR and were negative for minimal residual disease (MRD). An additional 13% of patients had a CR or stringent CR and were MRD positive or MRD could not be evaluated. The remaining responders had a very good partial response (19%) or a partial response (13%).

The median progression-free survival (PFS) was 18.3 months, and the median overall survival (OS) was not reached. 

For patients with a CR or better at 3 months after CAR T-cell infusion, the 1-year PFS rate was 89%, and the 2-year PFS rate was 67%. This group had a 1-year OS rate of 92% and a 2-year OS rate of 84%.

The rate of cytokine release syndrome (CRS) was 95%, and 10% of patients had grade 3 or higher CRS. Neurotoxic events were observed in 11% of patients, and 3% had grade 3 or higher neurotoxicity.

All patients developed B-cell aplasia, and a majority developed neutropenia (98%), anemia (94%), or thrombocytopenia (79%). The researchers noted that side effects beyond 3 months were uncommon, except for B-cell aplasia (30%), hypogammaglobulinemia (42%), and infection (41%). 

“Long-term follow-up data show that the combination of anti-BCMA and anti-CD19 CAR T cells induces durable responses in patients with relapsed or refractory multiple myeloma, possibly by targeting less differentiated plasma cells and mitigating BCMA escape,” wrote JCO Associate Editor Suzanne Lentzsch, PhD, MD. “Dual CAR T-cell treatment was associated with a manageable long-term safety profile.” 

Reference

Wang Y, Cao J, Gu W, et al. Long-term follow-up of combination of B-cell maturation antigen and CD19 chimeric antigen receptor T cells in multiple myeloma. J Clin Oncol. Published online March 25, 2022. doi:10.1200/JCO.21.01676