BCMA-Targeting CAR T-Cell Tx Effective in R/R MM

The BCMA (B-cell maturation agent)-targeting chimeric antigen receptor (CAR) T-cell therapy bb2121 had promising efficacy at the active dose in patients with relapsed or refractory (R/R) multiple myeloma; updated results of the CRB-401 study (abstract 8007) were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

Lead author Noopur S. Raje, MD, of Massachusetts General Hospital Cancer Center, commented, “bb2121 at [an] active dose of greater than 150 million cells does induce deep and durable response in pretty heavily pretreated multiple myeloma patients.”

The agent bb2121 is a second-generation CAR T-cell therapy targeted against BCMA to redirect T cells to recognize and kill malignant myeloma cells.

CRB-401 is an ongoing, two-part study of bb2121 in R/R myeloma. In the dose-escalation part of the study, presented at the 2017 American Society of Hematology Annual Meeting, 21 patients had to have received three or more prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or have double-refractory disease and BCMA expression of 50% or more on plasma cells.

In the dose-expansion part of the study reported at ASCO, 22 patients were also required to have received daratumumab and be refractory to their last line of therapy. No BCMA expression was required, but about half of patients had BCMA expression of 50% or greater.

Previous results showed that a dose of 50 × 106 CAR T cells was ineffective and resulted in no T-cell expansion at all. Patients who received a dose between 150 million and 800 million cells had a “nice robust” expansion of the bb2121 product, according to Raje. This expansion persisted for close to 6 months and beyond in a subset of patients.

The overall response rate (ORR) in patients with low BCMA expression (100%) was similar to that of patients with high BCMA expression (91%).

Anybody who received 150 million or more cells had a very good overall response, Raje said. The ORR in patients who received the 150 million–cell dose was 57.1%; among patients who received doses greater than 150 million cells, the ORR was 95.5% and median duration of response was 10.8 months.

Among all patients who received the active dose of 150 million or more cells, the median progression-free survival (PFS) was 11.8 months. Median PFS was 17.7 months in patients with minimal residual disease–negative status.   

Raje said that although there was an overall cytokine release syndrome (CRS) rate of about 63%, the rate of significant CRS of grade 3 or higher was quite low, about 2%. Median time to CRS was 2 days (range, 1 to 25 days). Very few patients required tocilizumab or corticosteroids, Raje said.

“Compared to a lot of other CAR T-cell products, the neurotoxicity rate was fairly low,” Raje said. One patient experienced significant neurotoxicity but subsequently recovered, she said. There were no grade 4 CRS events and no fatal CRS or neurotoxicity events.

The abstract Discussant, Parameswaran Hari, MD, of the Medical College of Wisconsin, said these data are still early, and bb2121 does not yet provide a cure. “I will advise my patients who are in stringent CR and on maintenance [therapy] not to go for CAR T cells unless they relapse,” he said.