Idecabtagene: ASH 2022 Multiple Myeloma Madhav Dhodapkar KarMMa-2
By Madhav Dhodapkar, MBBS
What is Idecabtagene, and how can it help patients with multiple myeloma? The data that I’m gonna present at the ASH meeting this year is relates to a specific cohort of the KarMMa trial called KarMMa-2 Cohort 2c. And this is a cohort that involves patients who had achieved suboptimal response following autologous stem cell transplantations. These are myeloma patients that have gone through initial induction therapy and stem cell transplantation, but have not achieved a complete remission. And these people were treated with a single dose. Of Ide-Cell, which is a BCMA specific etic antigen receptor or CAR T-cell to see if that therapy would have efficacy in this setting. And so the this trial primarily is a description of the data that we’re finding from that cohort.
What is the standard of care for this disease state and what problem is the Idecabtagene trial attempting to solve?
The patients who do not achieve an adequate response following initial therapy have a poor outcome and do worse than others who actually do respond really well to initial therapy. So there’s really an unmet need to identify newer therapies in this patient population to see if we can actually get to complete responses, to deeper responses, and hopefully eventually cure. It’s clearly an unmet need that this study tries to fill.
The specific cohort again deals with patients who had a suboptimal response to initial therapy. And this is really a phase 2 study in the sense that our goal is to try to identify or characterize the response to this therapy in this specific cohort of patients and to see whether or not we’re able to achieve high rates of complete response or even molecular remissions in this patient population with this specific newer therapy called Ide-Cell.
What are the significant data points that oncologists need to know?
I think the top line messages, if you will, from in this trial that we’re gonna be presenting at this ASH meeting are that Ide-Cell led to very high rates of response. So 87% of patients responded to therapy, which is quite remarkable, out of which 74% of patients achieved a complete response are better, again, very remarkable. Plus these responses were quite durable, and certainly maintained in a great majority of patients for at least 2 plus years.
The other important finding from this study is the high rates of what we call molecular responses. So we achieve what we call MRD negative or minimal residual disease negative status in large proportion of patients as well as the fact that the safety or the tolerability of this therapy was actually quite good. And the rates of the typical side effects that we see with chimeric antigen receptor therapy, such as CRS or neurotoxicity rates were actually lower. Then we were, then were seen in prior studies with relapse refractory myeloma. So overall a positive efficacy good safety profile, and therefore, I think it suggests or makes the case for further testing of this specific therapy in this patient population.
Did this study meet its primary end point?
The objective was the study was to actually show high rates of response and absolutely, yes, it did meet its primary endpoint and it also in fact showed that this therapy is quite active in this patient population.
What questions have you received from oncologists and hematologist about this data?
So I think the major next set of questions is going to be relating to further evaluation of this specific compound or this specific therapy in this patient population. Design of randomized controlled trials to eventually get it to FDA approval. Ide-Cell is now already approved in patients in further lines of therapy, but this strikes to bring it to the beginning, if you will, and in patients who receive only one line of therapy.
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So that’s going to require additional testing comparisons with current existing therapies. And if it actually does prove to be superior in that setting, of course that would be the desired next step for this kind of, this line of therapy. I think the patients typically want therapies like this because it is a, sort of a one and done strategy, which does not require ongoing long-term therapy. So the, so there’s a lot of interest within our patients and within our community colleagues, to actually explore these kinds of options for our patients.
3 Key Takeaways from the Idecabtagene KarMMa-2 Clinical Trial
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In the phase 2 pivotal KarMMa study (NCT03361748), treatment with the B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel) resulted in frequent, deep, and durable responses in patients with relapsed and refractory multiple myeloma ((RRMM) hematologic malignancies) who were triple-class exposed and refractory to their previous treatment (Munshi N Engl J Med 2021).
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After lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 3), patients received a single infusion of 150–450 106 CAR+ T cells from ide-cel. Post-infusion, patients may get maintenance therapy at the discretion of the investigator.
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On or after ide-cel infusion, Grade (Gr) 3-4 adverse events (AEs) were recorded in 29 (93.5%) patients, most frequently febrile neutropenia in 25 (80.6%), leukopenia in 9 (29.0%), and anemia in 7 (22.6%).
What are the key takeaways oncologists and hematologists should know about this study?
So I think the key takeaway is that Ide-Cell seems to show promising data in the context of this specific cohort of patients that we just described. Patients who achieved suboptimal responses following initial induction therapy followed by stem cell transplants. And therefore there’s a potential that this kind of approach may in fact be a therapeutic option in the future for this group of patients.
Madhav Dhodapkar, MBBS – About The Author, Credentials, and Affiliations
Madhav V. Dhodapkar, MBBS, is the Anise McDaniel Brock Chair and Georgia Research Alliance Eminent Scholar in Cancer Innovation, as well as a professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine. Dr. Dhodapkar is the head of the Winship Center for Cancer Immunology and the leader of the Cancer Immunology Research Program at the Winship Cancer Institute.
Prior to joining Emory, he was Chief of Hematology, Arthur H. and Isabel Bunker Professor of Medicine (Hematology), and Professor of Immunobiology at Yale School of Medicine. He was an expert in the treatment of multiple myeloma and co-director of the Cancer Immunology Program at the Yale Cancer Center. I have also held professor posts at Myeloma Institute in Little Rock, Arkansas, Memorial Sloan Kettering Cancer Center in New York, New York, and The Rockefeller University in New York, New York.
The hematologist and medical oncologist Dr. Dhodapkar specializes in the treatment of multiple myeloma and other hematological cancers. His primary clinical and academic interests include the immuno-biology of multiple myeloma and the development of novel biological cancer treatments.