CAR T-cell therapy with BCMA-targeting idecabtagene-vicleucel (ide-cel) resulted in deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma, according to phase II data from the KarMMa trial (Abstract 8503).
With a median follow-up of 11.3 months, 73% of patients responded to treatment. The median progression-free survival (PFS) was 8.8 months. At 1 year, CAR-positive T cells were detected in more than one-third of patients.
“Overall, ide-cel provides an attractive and excellent option for treatment of triple-class exposed multiple myeloma,” said Nikhil C. Munshi, MD, of Dana-Farber Cancer Institute, who presented the results during the ASCO20 Virtual Scientific Program.
“Overall, ide-cel provides an attractive and excellent option for treatment of triple-class exposed multiple myeloma.” - Dr. Nikhil C. Munshi
The trial included patients with myeloma who had three or more prior regimens and were refractory to their last regimen. All patients had been previously exposed to an immunomodulatory agent, proteasome inhibitor, and an anti-CD38 antibody. Patients received doses between 150-450 x 106 CAR-positive T cells. The primary endpoint was overall response rate (ORR).
Of the 140 patients who underwent leukapheresis, 128 were treated. Eighty-eight percent of patients received bridging therapy during CAR T-cell manufacturing, “suggesting an aggressive nature of the disease for the patients entered on the study,” Dr. Munshi said. Only 4% of patients responded to bridging therapy.
Both the primary and secondary endpoints were met. ORR was 73% with a complete response (CR) rate of 33%. At the target dose of 450 cells, ORR was 82% with a CR rate of 39%. The median time to first response was 1 month, and the median time to CR was 2.8 months.
Looking at minimal residual disease (MRD) negativity, 26% of patients had MRD negativity and CR, and 39% had MRD negativity and very good partial response. Clinically meaningful efficacy was observed across subgroups, Dr. Munshi said (Figure).
The median duration of response was 10.7 months across all dose levels and improved to 11.3 months for the 450 million cell dose level. Duration of response was also increased with depth of response. The median duration of response was 19 months among patients who achieved CR.
PFS was 8.8 months. Again, PFS increased with an increase in dose and with depth of response. Among patients achieving CR, the median PFS was 20 months.
Overall survival was 19.4 months with 87% of patients treated with ide-cel event-free at 12 months. Survival data are still immature with 66% of patients censored overall, Dr. Munshi noted.
The most common any-grade adverse event was cytopenia. Cytokine release syndrome (CRS) occurred in 84% of patients but was mostly grade 1/2. Only 5% of patients had grade 3 CRS; one patient had grade 4, and one patient had grade 5. Neurotoxicity also occurred in 18% of patients; 3% had grade 3 neurotoxicity.
There were five deaths overall within the 8 weeks of ide-cel infusion; two occurred after myeloma progression and three from adverse events.
During her discussion of the results, Krina Patel, MD, MSc, of The University of Texas MD Anderson Cancer Center, pointed out that although KarMMa was one of first trials for BCMA-targeting CAR T-cell therapy, there are now more than 60 trials of BCMA CAR T-cell studies for multiple myeloma.
Although a variety of different subgroups within KarMMa responded to therapy, others didn’t.
“Dose level seems to have mattered,” Dr. Patel said. “In terms of ISS-3 patients, they still responded but maybe a little bit less of a response rate. For patients with high-risk disease, they actually had a good response rate with both high-risk cytogenetics and extramedullary disease.”
These results are exciting, she said, because these high-risk patients usually do not have many options that last very long.
Moving forward, other challenges still need to be resolved, Dr. Patel said. These include elucidating mechanisms of resistance, clarifying sequencing of combination therapies, improving patient access, and transitioning to outpatient treatment.
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