Ide-cel in Multiple Myeloma Post-Transplant: Insights From Garfall

Alfred L. Garfall, MD, director of Autologous Hematopoietic Stem Cell Transplantation, the section chief of Myeloma and Hematology-Oncology, and an associate professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania, Penn Medicine, in Philadelphia, discusses the phase 2 BMT CTN 1902 trial (NCT05032820) which evaluated the safety, feasibility, and effectiveness of idecabtagene vicleucel (ide-cel; Abecma), an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, in patients with multiple myeloma with suboptimal response after upfront autologous stem cell transplant.

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0:10 | So, this is a clinical trial that tests the use of ide-cel, an anti-BCMA CAR T-cell product, to improve response for patients who have been through the standard intensive first-line multiple myeloma therapy and have failed to achieve a complete response. That intensive first-line therapy that these patients have been through is some form of multi-agent induction therapy, followed by consolidation with high-dose melphalan and autologous stem cell transplant, and then some period of lenalidomide-based maintenance therapy. 

0:50 | That group of patients, if they after all that therapy, if they have failed to achieve a complete response, you know, that group of patients has, on average, inferior long-term outcomes. The idea was whether CAR T cells at that point, at this point in time, could convert patients to a complete response and hopefully improve their long-term outcomes.

1:17 | This was a phase 2, single-arm study that really focused on the safety and feasibility of this approach and a preliminary measure of effectiveness, which we based on the rate of conversion to complete response after 6 months after CAR T-cell infusion. The reason it was important to demonstrate initial safety and feasibility in a smaller study here is because there have not been many studies that have utilized CAR T cells early after an autologous stem cell transplant.

1:50 | We had questions about whether the T cells that you would harvest from patients early after transplant, if they could be used for CAR T-cell manufacturing in the setting where the myeloma is at a very low level, even though these patients haven't achieved a complete response, they have relatively low amounts of myeloma because of all the prior therapy they've had. And so whether CAR T cells, if they were infused into patients who had a low amount of myeloma, whether the CAR T cells really expand and have an anti-myeloma effect in this setting.

2:22 | And then, because it is a standard approach for these patients to be on long-term maintenance with lenalidomide, and at the same time, it's also common for patients after CAR T-cell therapy to have low blood counts, we wanted to make sure that it was feasible to get them back on lenalidomide maintenance therapy. Because we were concerned that, you know, when you combine the effect of the auto transplant on blood counts, and then CAR T-cell therapy on blood counts, and then lenalidomide's effect, that maybe we were concerned that we wouldn't be able—patients might not be able to resume the standard-of-care lenalidomide maintenance, which is an intervention that has been proven to prolong overall survival in [patients with] myeloma patients.

3:08 | So, a major objective of this study was to get a preliminary assessment of whether patients were able to resume lenalidomide after CAR T-cell therapy and continue the standard-of-care first-line therapy with lenalidomide maintenance.