COMy 2023 | The value of bispecific T-cell engager therapies in myeloma & future considerations for these agents
In this video, Luciano Costa, MD, PhD, UAB School of Medicine, Birmingham, AL, discusses the advantages and disadvantages of using novel bispecific T-cell engagers (BiTEs) to treat patients with multiple myeloma. Dr Costa explains that BiTEs have demonstrated high efficacy in heavily pre-treated patients, with response durations matched only by CAR-T cell therapy, and further notes that BiTEs are potentially easier to implement than CAR-T cells and may thus carry scalability advantages. Dr Costa concludes with summarizing the drawbacks of BiTEs that will require further investigation, including the complexity of administration and mitigating risk of cytokine release syndrome (CRS) and infection, and highlights the potential value of developing limited-duration therapeutic approaches. This interview took place at the 9th World Congress on Controversies in Multiple Myeloma (COMy) 2023, held in Paris, France.
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Transcript (edited for clarity)
So bispecific T-cell engagers are really on the cusp of I think, a revolution in how we treat myeloma patients. The excitement is perhaps only comparable to the one with CAR-T cells, but here you have several practical and scalability advantages since those are off-the-shelf products that are at least in theory much easier to implement on a larger scale of patients. So the responses and the duration of responses we have seen in patients who are heavily pretreated, it’s really only matched by CAR-T cell therapy...
So bispecific T-cell engagers are really on the cusp of I think, a revolution in how we treat myeloma patients. The excitement is perhaps only comparable to the one with CAR-T cells, but here you have several practical and scalability advantages since those are off-the-shelf products that are at least in theory much easier to implement on a larger scale of patients. So the responses and the duration of responses we have seen in patients who are heavily pretreated, it’s really only matched by CAR-T cell therapy. We have a lot of trials going on that are exploring those agents in earlier lines of therapy on first or second, third relapse and in several more that are being launched or being implemented testing those agents even as part of the initial therapy. In the past, things had a 20 to 30% response rate in later lines were transformative in early settings. So I can only imagine what class of agent with 60 to 70% response rate in later lines will do. Now that being said, there’s still a lot of things to be learned, a lot of caution to be exercised because those agents have somewhat of a complex administration initially in order to mitigate the risk of cytokine release syndrome and to the lesser extent neurotoxicity. But I think the major concern that is emerging with those agents, regardless of a specific product or target, is the risk of infection. And I think we have learned a lot about infection prevention and infection mitigation in myeloma over the last decades. But this is really a new chapter. I think the type and frequency of infections is really a different level that we still have to learn how to deal with. And problems like that and the high efficacy of those agents really call into action the necessity to develop approaches with limited duration of therapy, which was an opportunity that was not so high when the activity was less. But I think when we have such active agents, you really need to embrace the possibility of a fixed duration therapy and give the patients some hopefully long breaks when they are disease-free and treatment-free.
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