Noopur S. Raje
CHICAGO — Chimeric antigen receptor T-cell therapy bb2121 demonstrated continued efficacy and safety among patients with relapsed or refractory multiple myeloma, according to data from a two-part, ongoing, phase 1 trial presented at the ASCO Annual Meeting.
Results showed bb2121 (Bluebird Bio) — a second-generation chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) — induced deep and durable ongoing responses, with manageable cytokine release syndrome and neurotoxicity.
“CAR T-cell therapy is an exciting option for patients with myeloma. The bb2121 product has demonstrated safety and sustained efficacy in a highly relapsed refractory patient population,” Noopur S. Raje, MD, professor of medicine at Harvard Medical School and director of the Multiple Myeloma Center at Massachusetts General Hospital, told HemOnc Today.
The dose-escalation part of the trial included 21 patients (median age, 58 years) previously treated with three or more prior lines of therapy with a proteasome inhibitor and immunomodulatory agent or who were double refractory. All patients had 50% or more B-cell maturation antigen expression on plasma cells.
The dose-expansion part of the trial included 22 patients (median age, 65 years) who previously received daratumumab (Darzalex, Janssen Oncology) and were refractory to last line of therapy. B-cell maturation antigen expression was not required for this cohort.
Patients received one infusion of bb2121 after lymphodepletion with 30mg/m² fludarabine and 300mg/m² cyclophosphamide daily for 3 days. Researchers escalated bb2121 at four dose levels: 50 x 106 cells (n = 3), 150 x 106 cells (n = 12), 450 x 106 cells (n = 19) and 800 x 106 cells (n = 3).
Median follow-up for the dose-escalation cohorts was 35 weeks; 18 patients who received a dose of 150 x 106 cells or higher were evaluable for safety and efficacy.
Overall response rate for these 18 patients was 94%, including 56% who achieved complete remission or unconfirmed complete remission.
Median PFS was 11.8 months.
Sixteen patients appeared negative for minimal residual disease; for these patients, median PFS was 17.7 months.
Eighty-one percent of patients achieved 6-months PFS and 71% achieved 9-month PFS.
No dose-limiting toxicities or grade 3 or higher neurotoxicities occurred. Grade 1/grade 2 cytokine release syndrome occurred among 71% of the cohort and two patients experienced grade 3 or higher cytokine release syndrome that resolved in 1 day. Two patient deaths occurred — both patients achieved complete response and had not progressed on treatment.
Based on these data, researchers selected doses of 150 to 300 × 106 CAR T cells for the expansion phase.
“To date, the safety profile of bb2121 has been manageable at doses as high as 800 x 106 cells,” Raje said. “This data provides the impetus to study this approach in less refractory patients with myeloma.” – by Jennifer Southall
Raje NS, et al. Abstract 8007. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Raje reports consultant/advisory roles with Amgen, Bristol-Myers Squibb, Celgene, Merck, Novartis and Takeda, as well as research funding from AstraZeneca. Please see the abstract for a list of all other authors’ relevant financial disclosures.