CAR T-cell Therapy Impresses in Multiple Myeloma

A chimeric antigen receptor (CAR) T-cell therapy that targets the B-cell maturation antigen (BCMA) on myeloma cells triggered responses in most patients with relapsed or refractory multiple myeloma, according to updated clinical trial results presented at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, GA, held December 9–12.

At the 2017 American Society of Clinical Oncology Annual Meeting in June, researchers reported results from a phase I trial of the BCMA-targeting CAR T-cell therapy bb2121 (Bluebird Bio) in patients with relapsed or refractory multiple myeloma. The patients had had a median of seven treatments, including autologous stem cell transplants, before receiving an infusion of 50 million to 800 million CAR T cells. After a median follow up of 15.4 weeks, 71% of the 21 patients evaluated for safety had developed cytokine release syndrome (CRS). All 15 who received at least 150 million cells and were assessed for treatment efficacy responded to the therapy, with 27% showing complete responses.

At the ASH meeting, James Kochenderfer, MD, of the NCI offered data on those patients after a longer median follow-up period of 40 weeks, adding details on the treatment's effectiveness and safety. The rate of CRS remained at 71%, with the severity reaching grade 3 or above in only two people. One patient developed a delayed grade 4 neurologic toxicity but recovered. Five of the patients in the trial have died: The three patients who received the lowest dose of CAR T cells died after disease progression; two patients died from other causes (heart attack and myelodysplastic syndrome) while their disease was in remission.

Of the 18 patients who received higher doses, 17 responded to the treatment and 10 showed complete remissions. The median duration of progression-free survival (PFS) hasn't been met, but the PFS was 83% at 6 months and 73% at 9 months. A phase II trial, dubbed KarMMa, has been launched to test doses of between 150 million and 300 million CAR T cells, Kochenderfer said.

The results suggest that “targeting BCMA for multiple myeloma will be the next setting where CAR T-cell therapy has a dramatic effect,” said Eric Smith, MD, PhD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY. Smith wasn't connected to the study but has developed a different BCMA-targeting CAR T-cell therapy for multiple myeloma. “The biggest questions going forward are going to be the mechanisms of relapse and resistance,” he said.

Alexander Lesokhin, MD, also of MSKCC, agrees that the results are impressive. “A complete response rate greater than 50% in patients who have seen a median of seven lines of therapy is incredibly good.” But he noted that this CAR T-cell variety faces plenty of competition, not only from other BCMA-targeting CAR T-cell formulations that are already in clinical trials, but also from other types of treatment under development, including antibody–drug conjugates and bispecific antibodies. “The challenges for this particular therapy will be the side effect profile, and the logistical challenges and cost of delivering it,” he said. –Mitch Leslie