The FDA has granted Bluebird bb2121 a breakthrough therapy designation for previously treated patients with relapsed/refractory multiple myeloma, according to Celgene Corporation and bluebird bio, the companies developing the anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy.

In a press release, the companies reported that the investigational agent had also been awarded PRIority MEdicines (PRIME) eligibility by the European Medicines Agency (EMA). The FDA and EMA took action based on preliminary clinical data from the ongoing phase I CRB-401 study. The companies did not release any data, but noted that updating findings would be presented in December at the 2017 ASH Annual Meeting.

“Despite recent advances, multiple myeloma remains an incurable disease, and heavily pretreated patients have limited therapeutic options,” David Davidson, MD, chief medical officer for bluebird bio, said in a statement. “Early data suggest that treatment with bb2121 has the potential to induce durable responses in this patient population.”

Yi Lin, MD, PhD, assistant professor of medicine and oncology at the Mayo Clinic in Rochester, NY, presented early results from CRB-401 at the 22nd Annual European Hematology Association (EHA) Congress in June 2017. At that point, the objective response rate (ORR) was 100% (95% CI, 78.2-100) in 9 evaluable patients who were infused with bb2121 at a dose of 5.0 x 107 CAR-positive T cells or higher.

A total of 21 patients were treated in 5 dose cohorts from 5.0 x 107 to 120 x 107 CAR-positive T cells. The first response evaluation was done at 1 month post treatment.

Investigators hope to eventually enroll 50 heavily pretreated patients with multiple myeloma at 7 sites. The primary endpoint of the trial is the incidence of adverse events and abnormal laboratory test results, which include dose-limiting toxicities.

Eligible patients were required to have undergone at least 3 prior treatments, including a proteasome inhibitor and an immunomodulatory agent, or were double-refractory with ≥50% BCMA expression. Of the 21 patients treated thus far, all had undergone autologous stem cell transplant, and had a median of 7 (range, 3-14) prior therapies. The median patient age was 58 years and 62% were male. Two-thirds of patients had high-risk cytogenetic changes at baseline.

Most patients, 75%, demonstrated a very good partial response or better and 27% had complete response (CR). The evaluable patients at this dose level were minimal residual disease–negative.

The ORR across all dose levels was 89% (95% CI, 65-99). The median time to first response was 31 days, and the median time to best response was 50.5 days. The duration of response was 134 days and longer (95% CI, 7-361).

Patients underwent leukapheresis and a lymphodepletion conditioning chemotherapy regimen consisting of cyclophosphamide and fludarabine for 3 days followed by 2 days of rest before the CAR T-cell infusion. Their mononuclear cells were then shipped to a central facility for manufacturing.

All patients consistently demonstrated CAR-positive T-cell expansion. CAR T cells persisted in the blood up to 24 weeks and 68% were also detected in the bone marrow by flow cytometry.

M-protein was rapidly cleared from the serum in most patients as early as 4 weeks’ post infusion, as was free light chain, which was reduced from baseline by 100% by the time of the data cutoff in all but 2 patients. The change from baseline in serum BCMA by 4 weeks’ post infusion ranged from 80% to 100%.

Fifteen (71%) patients experienced cytokine release syndrome (CRS), 2 patients had grade 3 CRS that resolved within 24 hours, and 4 patients had grade 1/2 CRS; 4 patients received tocilizumab (Actemra) and one grade 1 CRS was treated with steroids. Two patients had pyrexia. Importantly, no cases of grade 3/4 neurotoxicity were reported.

Breakthrough therapy designation is intended to expedite the development and review of drugs that are intended to treat serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

The EMA initiated PRIME as a voluntary program that encourages development of medicines that target an unmet medical need. It is based on enhanced interaction and early dialogue with developers of promising medicines, to optimize development plans and speed up evaluation so these medicines can reach patients earlier.

"Receiving breakthrough therapy designation and PRIME eligibility for bb2121 further underscores the potential of this novel cellular immunotherapy approach to multiple myeloma treatment," Jay Backstrom, MD, chief medical officer and head of Global Regulatory Affairs for Celgene, said in a statement. "We will work closely with these agencies as we accelerate development of bb2121, a novel technology and therapy for patients with multiple myeloma."