Initial data from the ongoing phase I clinical trial of bb21217 (CRB-402) were presented at the 60^th Annual Meeting of the American Society of Hematology (ASH). This is an investigational next-generation anti-BCMA CAR T cell therapy being studied in patients with relapsed/refractory myeloma.

Bb21217 is an investigational anti-BCMA CAR T cell therapy, developed by Bluebird Bio and Celgen, that uses the bb2121 chimeric antigen receptor (CAR) molecule with a manufacturing process designed to improve CAR T cell functional persistence. Bb21217 has exhibited improved functional persistence and increased anti-tumor activity in preclinical animal studies.

This therapy is being evaluated in the ongoing dose escalation part of the phase I CRB-402 study in adults with relapsed/refractory myeloma who have received at least three prior treatments, including a proteasome inhibitor and immunomodulatory agent (or are double refractory).

“Patients with multiple myeloma often undergo multiple cycles of treatment because there is currently no known cure for this aggressive cancer,” said Nina Shah, M.D., University of California, San Francisco (USA). “The early clinical data from this phase I study show manageable safety findings, and most patients in this initial group achieved an objective response. Future study is needed to assess durability of response at the current dose, as well as safety and activity at higher doses of bb21217.”

Patients included in these preliminary phase I results (n=12) had a median age of 63 years (min; max: 44 – 69 years). They had received a median of seven prior lines of therapy (min; max: 4 – 17 lines) and 83 percent of patients received a prior autologous stem cell transplant. Fifty-eight percent (n=7) of patients had high-risk cytogenetics.

All treated patients received a dose of 150 x 10⁶ CAR+ T cells. The median follow-up after bb21217 infusion was 26 weeks (min; max: 4 – 51 weeks). The primary endpoint is safety measured by frequency of adverse events (AEs), dose limiting toxicity (DLT) and changes in laboratory results. Secondary endpoints include disease specific response criteria based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma.

Efficacy and safety results

Of the 12 patients who received treatment with bb21217, 83 percent (n=10) achieved an objective clinical response by IMWG criteria. As of the data extract, responses are ongoing in nine of 10 patients, including three with a complete response (CR) or stringent complete response (sCR), two with a very good partial response (VGPR) and four with a partial response (PR).

Evidence of myeloma in the bone marrow, known as minimal residual disease (MRD), was undetectable at a minimum of two time points, by next-generation sequencing at a sensitivity level of 10^-5 or better in all responders who had evaluable bone marrow samples (n=4) with some as early as day 15.

The safety results were manageable and consistent with known toxicities of CAR T therapies. Eight of the 12 patients (67 percent) treated with bb21217 developed cytokine release syndrome (CRS); four Grade 1, three Grade 2, one Grade 3 case and no Grade 4 cases. Additionally, three of the 12 patients (25 percent) experienced neurotoxicity, including one Grade 1, one Grade 2 and one Grade 4 case.