Interim results from CRB-401, an ongoing phase 1 study of bb2121 - a BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy candidate for patients with relapsed and refractory multiple myeloma - were published in the New England Journal of Medicine (NEJM). 

The manuscript, "Anti-BCMA CAR T Cell Therapy bb2121 in Relapsed/Refractory Multiple Myeloma" includes key safety and efficacy results from the dose escalation and first expansion cohort, including a minimum of six months follow up on all subjects.

As of the data cut-off date of April 30, 2018, manageable safety and deep and durable responses were reported in the first 33 patients infused with bb2121 BCMA-targeted CAR T-cells.

Patients in the study were heavily pre-treated, with a median of seven prior multiple myeloma treatment regimens (range, 3 to 23), which included prior treatment with immunomodulatory drugs, proteasome inhibitors and daratumumab in the majority of patients.

All but one patient had previously received an autologous stem cell transplant.

"CAR T-cell therapy is an important area of research for relapsed/refractory multiple myeloma patients where there remains a need for new options. We are encouraged by the expansion and persistence of the CAR T-cells, as well as the deep and durable responses with a manageable safety profile we've seen for bb2121 to date," said senior author and principal investigator James N. Kochenderfer, M.D., Experimental Transplantation and Immunology Branch, National Cancer Institute Center for Cancer Research.

For the first 33 patients, the most common grade ≥ 3 events were haematologic toxicities, including neutropenia (85%), leukopenia (58%), anaemia (45%) and thrombocytopenia (45%).

Neurotoxicity all-grades occurred in 14 (42%) patients; 13 (39%) were grade ≤ 2 and one patient (3%) had grade 4 neurotoxicity which resolved within one month.

Twenty-five (76%) patients experienced cytokine release syndrome; 23 (70%) were grade ≤ 2 events and two (6%) were grade 3 events; all events were reversible.

Infection occurred in 14 (42%) patients; two were grade 3 (6%) and there were no grade 4 events.

Peak CAR T cell expansion was higher in patients with cytokine release syndrome and CAR T-cells remained detectable in the blood in 57% of patients at six months following infusion.

Treatment with bb2121 resulted in an 85% objective response rate (ORR) with 45% of patients achieving a complete response (CR) (n=15) and an additional 27% of patients (n=9) achieving a very good partial response (VGPR) to yield a ≥ VGPR rate of 73%.

Sixteen responding patients were evaluable for assessment of minimal residual disease (MRD) and all tested MRD negative at one or more time points.

Responses to bb2121 CAR T-cell infusion occurred early, with a median time to first partial response or better of 1.0 month (range, 0.5 to 3.0), and responses were durable, with a median duration of response of 10.9 months (95% CI, 7.2 to not estimable).

Researchers observed that greater CAR T-cell expansion occurred in responding patients.

Responses were observed independent of tumour or serum BCMA levels.

Median progression-free survival among all 33 patients was 11.8 months (95% CI, 6.2-17.8).

"These data from CRB-401 demonstrate that BCMA is a promising target in the treatment of patients with multiple myeloma. We continue to be encouraged by the potential of bb2121 as a first-in-class BCMA-targeted CAR T-cell therapy," said Alise Reicin, M.D., President, Global Clinical Development for Celgene.

"The compelling data in these heavily pre-treated relapsed/refractory patients has provided important insights in the development of bb2121 as we continue the follow up of patients in our recently fully enrolled pivotal KarMMa trial. We are also evaluating the potential for bb2121 in earlier lines of multiple myeloma treatment in the other KarMMa trials."

"The data published in NEJM from CRB-401 provide the foundation for advancing the development of bb2121, which is currently being assessed in multiple clinical studies across different patient populations within multiple myeloma," said Dave Davidson, M.D., chief medical officer, bluebird bio. "We hope that this potentially first-in-class BCMA-targeted CAR T-cell therapy may provide a new treatment option for patients living with multiple myeloma."

In November 2017, bb2121 was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration and PRIority Medicines (PRIME) eligibility by the European Medicines Agency based on preliminary clinical data from the phase 1 CRB-401 study.

Potential approval of bb2121 in the U.S. is anticipated in the second half of 2020. bb2121 is an investigational therapy; safety and efficacy have not yet been established. bb2121 has not been approved for use by any health authority.

Source: DNA Communications