Recently, the FDA approved idecabtagene vicleucel (Abecma®, Bristol Myers Squibb) for patients with relapsed or refractory multiple myeloma who have already been treated with four or more lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The approval was based on KarMMa, a phase 2 trial that confirmed the efficacy and safety of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. In this interview, one of the study investigators, Nina Shah, MD, a hematologist-oncologist at University of California San Francisco Health, speaks with Oncology Data Advisor about the management of relapsed/refractory multiple myeloma, efficacy and adverse event management for idecabtagene vicleucel, and the ongoing evolution of multiple myeloma treatment.
What are the most significant challenges of managing relapsed or refractory multiple myeloma?
Nina Shah, MD: The most significant challenges with this disease are that it's incurable and it ultimately progresses to where the patient cannot be functional anymore, so it's really important for us to find treatments that will keep the patient as disease-free as possible and with a good quality of life.
Can you comment on the significance of the FDA's recent approval of idecabtagene vicleucel?
Dr. Shah: As myeloma physicians, we're all very excited about the FDA approval of idecabtagene vicleucel, which represents a first-in-class cellular therapy. It's a different type of immunotherapy in that it takes advantage of the patient's own immune cells, their own T cells, and engineers them to specifically attack the myeloma. This is the first time we've had this type of therapy available for multiple myeloma; this type of therapy has already been FDA approved for lymphoma.
The reason we're so excited about it is that in very heavily pretreated patients, idecabtagene vicleucel resulted in a very significant response rate––over 70%––and that's not usually seen in patients who are so sick with multiple myeloma. In addition, patients who got the targeted cell dose had a median progression-free survival of about a year. That's a year without additional therapy, which is something that has not been seen in myeloma before. Usually, myeloma patients get treated every week or every other week, and they're just chronically going to some sort of infusion or taking some sort of medication, but these patients made it a median of a year without having to take additional chemotherapy. So that's something that we've been very excited about, and we hope that we can actually even have better outcomes in the real world.
What adverse events are concerning with the regimen, and how can clinicians best manage those?
Dr. Shah: As is true with all cellular therapies, all chimeric antigen receptor (CAR) T-cell therapies, there's always a risk of cytokine release syndrome, also known as CRS. This did happen in over 80% of patients in the pivotal trial that got idecabtagene vicleucel approved, but it was fairly manageable, grade 1 or 2, and usually treatable with a drug called tocilizumab, and if not tocilizumab, then with steroids. So that was something that was manageable and treatable. Similarly, there are always concerns about neurotoxicity with CAR T cells. Again, this happened, although only in 18% of patients, and again was generally grade 1 or 2. So the safety profile of this product is actually very encouraging. I think that even people who did not participate in the clinical trials will be able to manage this with general ease after getting used to the workflow.
How do you see the treatment of relapsed/refractory multiple myeloma evolving?
Dr. Shah: I think that we will all think about at what point to use idecabtagene vicleucel. The FDA label states that it should be after four lines of therapy. So we will start to plan that and understand that if patients make it through their first or second line, we should be thinking and discussing with patients that after the third or fourth line, we can send them to CAR T-cell therapy. This also helps us to plan their chemotherapy regimen; if we are planning to proceed with CAR T-cell therapy, perhaps we want to use therapies that will not be too toxic to the patient's own T cells, because eventually we're going to send those cells off to be engineered. So I think we're going to start rethinking how we choose our therapies and how we sequence them so that the patient can ultimately receive this very effective therapy.
About Dr. Shah
Nina Shah, MD, is a Professor of Clinical Medicine and a hematologist-oncologist with University of California San Francisco Health. She specializes in blood diseases, with a focus on treating multiple myeloma. Dr. Shah is also a multiple myeloma researcher; she has authored numerous publications on that topic and has presented her research at multiple American Society of Clinical Oncology (ASCO) Annual Meetings. Dr. Shah is a member of ASCO, the American Society of Hematology (ASH), and the American Society for Transplantation and Cellular Therapy.
For More Information
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.