Immuno-Oncology Resource Center
Immuno-Oncology Resource Center
May 01, 2019
2 min read

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

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Noopur Raje, MD
Noopur Raje

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 published in The New England Journal of Medicine.

“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, told HemOnc Today. “[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).


Twenty-five patients experienced cytokine release syndrome (grade 1 or grade 2, n = 23; grade 3, n = 2), and 14 patients experienced neurologic toxic effects, one of which (grade 4) was reversible.

“A completed phase 2 trial needs to demonstrate similar toxicity profile and efficacy, [which] should allow approval [by the FDA],” Raje said. “Then, obviously, the work on cellular therapy [continues] where we have to figure out ways of sustaining responses and treating early.” – by John DeRosier

For more information:

Noopur Raje, MD, can be reached at Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114; email:

Disclosures: Raje reports personal fees for advisory board roles from Amgen, Celgene, Janssen and Takeda. Please see the study for all other authors’ relevant financial disclosures.