Investigational CAR T-Cell Therapy, bb2121, Shows Durable Responses in Relapsed or Refractory Multiple Myeloma

Wayne Kuznar

August 2018, Vol 9, No 2 | Payers’ Perspectives In Oncology: ASCO 2018 Highlights - Immunotherapy, Multiple Myeloma


Chicago, IL—The second-generation chimeric antigen receptor (CAR) T-cell therapy bb2121, engineered to target B-cell maturation antigen (BCMA), a protein on the surface of certain myeloma cells, displayed continuing efficacy and safety in an update of a phase 1 clinical trial in patients with relapsed or refractory multiple myeloma, according to data presented at ASCO 2018. Currently, no CAR T-cell therapy has been approved for patients with multiple myeloma.

The median progression-free survival (PFS) among the 18 patients who received an infusion of >150 × 106 CAR T-cells of bb2121 in the dose-expansion phase was 11.8 months, said Noopur S. Raje, MD, Clinical Director, Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, who presented the study’s results.

The CAR product “is essentially an autologous T-cell, which is transduced using a lentiviral encoding vector for a CAR, which is specific to human BCMA,” said Dr Raje. The co-stimulatory domain that includes 4-1BB is believed to be associated with durable CAR T-cell persistence compared with the CD28 co-stimulatory domain.

“What we’ve been able to show is that bb2121 at active doses of >150 × 106 cells does induce deep and durable responses in pretty heavily pretreated multiple myeloma patients,” she said. “It didn’t matter whether you had low or high BCMA expression; patients still responded.”

Study Details

In the dose-escalation portion of the study, the results of which were presented previously, 21 patients were included. The dose-expansion phase included 22 patients, 18 of whom received a dose of ≥150 × 106 CAR T-cells and were evaluable for safety and efficacy. The patients underwent leukapheresis and were then infused with CAR T-cells bb2121 after a lymphodepletion regimen. The dose of bb2121 was started at 50 × 106 CAR T-cells and was escalated to a maximum of 800 × 106 CAR T-cells. A total of 10 patients with low BCMA expression were included in the dose-expansion cohort.

The patient population was heavily pretreated, said Dr Raje. The median number of previous lines of treatment was 7 in the dose-escalation phase and 8 in the dose-expansion phase. All patients had previously received bortezomib (Velcade); 91% of patients in the escalation phase and 96% in the expansion phase received carfilzomib (Kyprolis), and 100% of patients had previously received lenalidomide (Revlimid).

“Anybody who got more than 150 × 106 cells all the way up to 800 × 106 cells had a nice, robust expansion of the bb2121 CAR T-cell product,” Dr Raje said. “This expansion persisted for close to 6 months and beyond in a subset of patients.” The patients who responded to the therapy had greater expansion of T-cells.

The median follow-up was 345 days in the escalation phase and 87 days in the expansion phase. The objective response rate (ORR) was 33% in patients who received 50 × 106 cells, which increased to 95.5% in those who received >150 × 106 cells.
Robust responses were seen in patients with low BCMA expression and in those with high BCMA expression (ORRs of 100% and 91%, respectively). The median PFS in the overall cohort of patients who received >150 × 106 cells was 11.8 months, which increased to 17.7 months in those who achieved negative minimal residual disease.

The overall rate of cytokine release syndrome (CRS) was 63% (5% were grade 3), and neurotoxicity occurred in 33% of patients (2% with grade ≥3). The median time to CRS was 2 days. There were no grade 4 CRS events. Tocilizumab (Actemra) was required in 21% of patients who had CRS. By dose level, the rate of CRS was 39% in patients who received 150 × 106 cells and 82% in those who received >150 × 106 cells. No fatal treatment-related toxicities were observed.

A pivotal global clinical trial called KarMMa is ongoing with bb2121, and additional trials are planned in multiple myeloma, including patients with earlier stages of disease.