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Idecabtagene Vicleucel Promising in Pretreated Myeloma

December 30, 2021

Three-quarters of patients with heavily pretreated multiple myeloma responded to treatment with the B-cell maturation antigen (BCMA)−targeted chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel), according to phase I results presented at the 2020 ASH Annual Meeting. Cytopenias and cases of cytokine release syndrome (CRS) were common, but generally low-grade, added lead author Yi Lin, MD, PhD, from Mayo Clinic in Rochester, Minnesota, who presented these results.

"With the longer follow-up, we are continuing to see a deep and durable response with ide-cel in heavily pretreated myeloma populations," Dr. Lin said. "For ongoing responders, a duration of response longer than two years has been seen."

The trial is a two-part phase I dose-escalation and dose-expansion study. The expansion phase included patients who had received three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, and whose disease was refractory to the last line of therapy.

After lymphodepletion with fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day for three days followed by two days of rest, patients received ide-cel (formerly known as bb2121) at target doses of 50, 150, 450, or 800×106 cells in the dose-escalation phase, and 150 or 450×106 cells in the dose-expansion phase. Safety was the study's primary endpoint.

At the data cut-off of April 21, 2020, 62 patients had been treated: 21 in the dose-escalation phase and 41 in the dose-expansion phase. Dr. Lin noted that the manufacturing success was 100%, with about half of the patients requiring bridging therapy while their CAR T cells were being manufactured.

The participants generally had a disease with a poor prognosis upon study entry, with 27% having high-risk cytogenetics and 76% having myeloma that was refractory to the last line of therapy.

Response was first assessed four weeks after infusion, and, at a median follow-up of 18.1 months, 11 patients (17.7%) were still on study.

"Not surprisingly, cytopenias are the most common adverse events of any grade and the most severe adverse events," Dr. Lin said (see TABLE).

For patients who did not have recovery of blood counts by one month after infusion, the median time to recovery of grade 3/4 neutropenia and thrombocytopenia was 1.9 and 2.2 months, respectively. There was one death within eight weeks of infusion in a patient who developed grade 2 CRS and cytopenias, but the death was not considered treatment related. Seven additional deaths occurred within six months of ide-cel, the majority of which (n=6) were due to myeloma.

Dr. Lin said there was a trend for more CRS with increased dose. However, there were no grade >3 CRS events, and grade 3 CRS occurred in only 6.5% of patients. The median time to onset of CRS was two days and median duration was five days. There was low use of tocilizumab (29%) and steroids (16.1%) to manage CRS. Most cases of neurologic toxicity were grade 1 and had a limited duration of three days However, one patient had grade 4 neurologic toxicity. Corticosteroid use to manage these symptoms was low (8.1%), as well.

She also reported preliminary efficacy data, noting that, "in this heavily pretreated population we are seeing impressive response rates."

The overall response rate was 76%, with a rate of complete response (CR) or better of 39%. Researchers observed a dose-related increase in response rate, and none of the 15 patients who achieved CR or greater had measurable residual disease detected in bone marrow (≤10-4 sensitivity).

Across all dose levels, the median duration of response was 10.3 months, and half of the eight ongoing responders had duration of response longer than two years. Dr. Lin added that duration of response was similar among patients with high-risk disease, including older patients and those with extramedullary disease.

In a survival analysis, the median progression-free survival was 8.8 months and median overall survival was 34.2 months among patients treated with doses higher than 150×106. Given these safety and efficacy data, the recommended phase II dose was 450×106.

"These results are exciting for a single-dose treatment with no maintenance therapy," Dr. Lin said, adding that long-term follow-up is needed to better understand survival outcomes with this treatment.

Study authors report relationships with Celgene and bluebird bio, which sponsored the trial.


Lin Y, Raje NS, Berdeja JG, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study. Abstract #131. Presented at the 2020 American Society of Hematology Annual Meeting, December 5, 2020.


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