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Noopur S. Raje, MD
Photo by Andrew D. Bowser

CHICAGO—bb2121, the anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, induced deep and durable ongoing responses in heavily pretreated multiple myeloma (MM) patients, updated results of a phase 1 study show.

At active doses (≥150 x 108 CAR+ T cells), the B-cell maturation antigen (BCMA)-targeted therapy produced an overall response rate of 95.5%, including a 50% rate of complete response (CR) or stringent CR, with a median duration of response of 10.8 months.

Median progression-free survival (PFS) was 11.8 months in the dose-escalation cohort.

Noopur S. Raje, MD, of the Massachusetts General Hospital Cancer Center in Boston, reported these results at the 2018 ASCO Annual Meeting (abstract 8007*). The study is sponsored by Celgene Corporation and bluebird bio.

To date, bb2121 has been manageable for patients at doses as high as 800 x 108 CAR T cells, Dr Raje noted.

She updated the findings of CRB-401 (NCT02658929), which included 43 patients with relapsed/refractory MM, including 21 in a dose-escalation (DE) cohort and 22 in a dose-expansion (Exp) cohort.

Patients received one infusion of bb2121 anti-BCMA CAR T cells after a lymphodepleting conditioning regimen including fludarabine and cyclophosphamide.

Patients were a median age of 58 (range, 37 – 74) and 65 (range, 44 – 75) in the DE and Exp cohorts, respectively.

Eight patients (38%) in the DE cohort and 9 (41%) in the Exp cohort had high-risk cytogenetics and had received a median of 7 (range, 3 – 14) and 8 (range, 3 – 23) prior regimens, respectively.

All patients in the DE cohort and 86% in the Exp cohort had a prior autologous stem cell transplant (ASCT), and 29% and 23% in each cohort, respectively, had more than one ASCT.


Patients in the DE cohort had a median PFS of 11.8 months at active doses.

All 16 responding patients who were evaluable for minimal residual disease (MRD) achieved MRD negativity and had a median PFS of 17.7 months.

The investigators observed a dose-response relationship across the active dose ranges and higher peak CAR T expansion in responding patients compared with those who did not respond.

The investigators also noted that the tumor response was independent of tumor BCMA expression.

bb2121 persisted for 6 months or longer in 44% of responding patients.

“This should be tested a little bit earlier now, because what we’ve done here is show the proof of concept, and really treated these very end-stage myeloma patients,” Dr Raje observed.

Adverse events of interest

“We found that this product is extremely well tolerated,” Dr Raje said. “We saw, certainly, cytokine release syndrome (CRS) in over 60% of patients, but most of the CRS was managed, and it was grade 1 and 2 with very little grade 3 CRS. [W]e just had 1 patient with grade 4 neurotoxicity who is now completely recovered.”

The 2 grade 3 CRS events observed in this study resolved in 24 hours, Dr Raje noted.

Infused patients (n=43) also experienced neutropenia (81%), thrombocytopenia (61%), and anemia (56%).

Thirty-one of 40 patients (78%) recovered their absolute neutrophil count to 1000/μL or greater by day 32, and 22 of 40 (55%) patients recovered their platelet counts to 50,000/μL or greater by day 32.


BCMA is the “latest promising target” in MM, said Parameswaran Hari, MD, of the Medical College of Wisconsin in Milwaukee, and this bb2121 data represents the largest and most mature experience with the CAR T approach in the disease.

However, patients are still relapsing, and the meaning of MRD negativity is unclear in this setting, Dr Parameswaran said in a presentation referencing the results of the study.

“Unfortunately, this is not yet a cure, so I’m going advise my patients who are in stringent CR and on maintenance not to go for CAR T cells unless they relapse,” he said.

An ongoing global trial of bb2121, known as KarMMa, is open for enrollment in North America and Europe, and additional studies are planned in earlier lines of myeloma.

*Data presented at the meeting differ from the abstract. 

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