CAR T-cell therapy bb2121 shows promising efficacy, manageable toxicity in multiple myeloma

A chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen produced high response rates with manageable toxicity among patients with heavily pretreated relapsed or refractory multiple myeloma, according to results of a phase 1 study. “The adverse events noted in our study were very manageable, and we saw low rates of cytokine release syndrome and neurotoxicity,” Noopur Raje, MD,director of the Center for Multiple Myeloma at Massachusetts General Hospital and professor of medicine at Harvard Medical School.

“[The toxicity] was manageable to the extent that we are now thinking [forward to] outpatient settings. Response rates were high, but we did not see a plateauing of responses in very late-stage multiple myeloma.”

The CAR T-cell therapy bb2121 (Celgene, Bluebird Bio) has shown promise in preclinical studies for treatment of multiple melanoma, for which new therapies have prolonged survival but failed to prevent relapse.

Raje and colleagues reported results from the first 33 patients (median age, 60 years, range, 37-75; men, n = 21) with relapsed or refractory multiple myeloma who received bb2121 in the dose-escalation (n = 21) and dose-expansion (n = 12) phases of the open-label, multicenter trial. All patients had received at least three previous lines of therapy that included a proteasome inhibitor and an immunomodulatory agent or were double refractory. All patients in the dose-escalation cohort and two patients in the dose-expansion cohort had tumor B-cell maturation antigen (BCMA) expression of 50% or greater.

After undergoing lymphodepletion with fludarabine and cyclophosphamide, patients received bb2121 as a single infusion at doses of 50 x 10⁶, 150 x 10⁶, 450 x 10⁶ or 800 x 10⁶ CAR-positive T cells in the dose-escalation phase and 150 x 10⁶ to 450 x 10⁶ CAR-positive T cells in the expansion phase.

Safety served as the primary endpoint. Data cutoff occurred 6.2 months after the last infusion.

Results showed an objective response rate of 85% (95% CI, 68.1-94.9), with 15 patients (45%) achieving a complete response, six of whom have since relapsed.

Median PFS was 11.8 months (95% CI, 6.2-17.8).

Sixteen patients with partial or complete responses appeared negative for minimal residual disease ( 10^-4 nucleated cells).

All 33 patients experienced adverse events, including 28 (85%) who experienced a grade 4 event.

The most common grade 4 hematologic adverse events included neutropenia (n = 26), leukopenia (n = 13), thrombocytopenia (n = 10) and lymphopenia (n = 9). Grade 3 hematologic adverse events included anemia (n = 15), leukopenia (n = 6) and thrombocytopenia (n = 5).

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Source: https://www.healio.com/hematology-oncology/myeloma/news/online/%7Bda1d1336-ff71-467d-a93d-3af4e6294cd5%7D/car-t-cell-therapy-bb2121-shows-promising-efficacy-manageable-toxicity-in-multiple-myeloma