Precision CAR-T Trial Shows Early Signs of Success in Multiple Myeloma

Interim data analysis of a phase 1 trial of chimeric antigen receptor-T (CAR-T) cells targeting the B-cell maturation antigen (BCMA) in heavily pretreated patients with relapsed/refractory multiple myeloma has identified an objective anti-tumor response, with limited toxicity.

According to a press release by bluebird bio, which is developing the drug in collaboration with Celgene Corporation, the open-label trial is investigating the clinical impact of bb2121 anti-BCMA CAR-T cells, with phase 1 primary endpoints of incidence of adverse events and abnormal laboratory test results, including dose-limiting toxicities. Other data that the trial seeks to assess at this early stage include complete response, very good partial response, and partial response, as well as establish a recommended dose for future trials.

The study enrolled a total of 11 patients, who were dosed in 4 dose cohorts: 5.0 x 10⁷, 15.0 x 10⁷, 45.0 x 10⁷, and 80 x 10⁷ CAR-T cells. Patients had received, and failed, a median of 6 prior treatments; all had received a prior autologous stem cell transplant. Sixty-four percent of patients had received daratumumab or a CD38 antibody.

At the interim analysis, all 11 patients were eligible for safety evaluation, but only the first 9 enrolled were evaluable for efficacy, and underwent restaging. Prior to being infused with bb2121 anti-BCMA CAR-T cells produced from the patient’s own blood, patients received a conditioning regimen of cyclophosphamide and fuldarabine, similar to the trial by Juno Therapeutics, which was halted just last week following a report of additional patient deaths due to cerebral edema.

The overall response rate was a 100% in patients administered the dose of 15.0 x 10⁷ and 45.0 x 10⁷ (which was the highest dose in the 9 evaluable patients). Of the 3 patients given the lowest dose of 5.0 x 10⁷ cells, a 50% reduction in disease symptoms was noted in at least 1 patient. In addition, a partial response was observed in the remaining 6 patients in the 2 other higher dose cohorts—importantly, 2 of the 6 patients were negative minimal residual disease.

David Davidson, MD, chief medical officer, bluebird bio, released a statement saying the company is pleased with the early results. “We are also encouraged by the safety profile to date, particularly the lack of severe cytokine release syndrome or neurotoxicity,” he added.

The trial results were presented today at the 28th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany.