Combined Anti-CD19 and Anti-BCMA CAR-T Therapy Feasible for Relapsed/Refractory MM

The combined infusion of humanized anti-CD19 and anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cells is feasible for patients with relapsed or refractory multiple myeloma (MM), according to results from a phase 2 trial published in The Lancet Haematology (2019 Aug 1. Epub ahead of print).

“Anti-[BCMA]…CAR T-cell therapy has been shown to have activity in patients with relapsed or refractory multiple myeloma. Reports have suggested that a small subgroup of less differentiated myeloma clones express CD19 and anti-CD19 CAR T-cell therapy has shown activity in some of these patients,” explained Zhiling Yan, MD, Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China, and colleagues.

This information led Dr Yan and colleagues to conduct a phase 2 trial assessing the safety and activity of combining anti-CD19 with anti-BCMA CAR T-cells for the treatment of patients with relapsed or refractory MM at the Affiliated Hospital of Xuzhou Medical University in China.

To be eligible for the trial, patients had to be aged 18 to 69 years, have histologically confirmed MM, have a Karnofsky Performance Score of ≥50 points, and meet the International Myeloma Working Group diagnostic criteria for relapsed or refractory disease.

Before CAR T-cell infusion, fludarabine 30 mg/m2 once daily for 3 days and cyclophosphamide 750 mg/m2 were used to deplete lymphocytes. The humanized anti-CD19 CAR T-cells and murine anti-BCMA CAR T-cells were each infused at 1x106 cells per kg.

The primary outcome of the study was the proportion of patients who achieved an overall response.

A total of 22 patients were enrolled in the trial between May 1, 2017, and January 20, 2019; of these patients, 21 received an infusion of CAR T-cells and were deemed evaluable.

At a median follow-up of 179 days, 20 (95%) of 21 patients achieved an overall response, including 9 (43%) stringent complete responses, 3 (14%) complete responses, 5 (24%) very good partial responses, and 3 (14%) partial responses.

The most common adverse event was cytokine release syndrome (n = 19), and the most common serious adverse events were hematologic toxicities, which occurred in 20 (95%) of the 21 evaluable patients in the study. The most common grade ≥3 adverse events included neutropenia (n = 18), anemia (n = 13), and thrombocytopenia (n = 13).

Dr Yan and colleagues noted that 1 patient died of cerebral hemorrhage related to sustained thrombocytopenia.

“Our results confirm that combined infusion of humanised anti-CD19 and anti-BCMA CAR T cells is feasible in patients with relapsed or refractory multiple myeloma, and the preliminary activity observed warrants further investigation in randomised trials,” Dr Yan and colleagues concluded.

“This dual CAR-T cell combinations might be a promising treatment option for relapsed or refractory multiple myeloma,” they added.—Janelle Bradley