A single treatment with a second-generation CAR T-cell treatment elicited an overall response rate of 94% in a small study of patients with heavily pretreated multiple myeloma, according to the results of a phase I (abstract 740) study presented at the 59th American Society of Hematology Annual Meeting and Exposition, held December 9–12 in Atlanta.
The treatment—called bb2121—targets B-cell maturation antigen (BCMA) to redirect T cells to myeloma cells.
“BCMA is a promising target for multiple myeloma,” said James N. Kochenderfer, MD, of the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland, who presented the results. “It is expressed nearly universally on multiple myeloma cells and its expression is restricted to plasma cells and a subset of B cells.”
The phase I, multicenter study included 24 patients who underwent leukapheresis. Manufacturing of the CAR T cells took 10 days. Three patients had clinical deterioration, which led to dosing in only 21 patients.
Treatment started at a low dose (50 million total flat dose of CAR T cells), which was escalated up in a 3 + 3 manner to 150 million, 450 million, and then 800 million. First response assessment occurred at 4 weeks. The primary objective of the study was to identify the maximum tolerated dose.
Kochenderfer noted that the patients were heavily pretreated with a median of seven prior lines of therapy.
Overall the treatment was well tolerated. There were no dose-limiting toxicities observed in the dose escalation period. Seventy-one percent of patients had cytokine release syndrome, but only 10% had grade 3 or higher. Twenty-four percent of patients experienced neurotoxicity, but none were grade 3 or higher.
“The neurotoxicity was generally much milder and less prevalent than I have seen in previous CAR T-cell studies,” Kochenderfer said.
Five deaths occurred. Three of these deaths occurred at the 50 million dose and were due to disease progression. Two deaths occurred at the “active” dose levels: one from myelodysplastic syndrome and one from cardiac arrest.
“Patients treated at the lowest dose level did not have good outcomes, with progressive disease in all three patients,” Kochenderfer said.
Among patients on the active doses, 17 out of 18 (94%) had overall response, and 10 of 18 patients obtained complete remission. At 52 weeks, five patients had met the 1-year progression-free survival standard, and there are durable, ongoing responses of longer than 1 year in many patients. The longest response is 58 weeks.
In addition, Kochenderfer noted, responses continued to improve as late as month 15. The median progression-free survival has not been reached.
An expansion cohort of 12 patients has begun. Kochenderfer noted that within this group there was one case of delayed onset, reversible grade 4 neurotoxicity associated with tumor lysis syndrome and cytokine release syndrome. It occurred in the patient with the highest tumor burden, who recovered completely and has obtained a very good partial response despite low BCMA in myeloma cells.