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COMy 2022 | Understanding mechanisms of resistance to immunotherapies in myeloma

In this video, Paola Neri, MD, PhD, University of Calgary, Calgary, AB, Canada, shares some highlights from a session at COMy 2022 which focused on mechanisms of resistance to immunotherapies in myeloma. Dr Neri explains that there are two major factors that can cause resistance in myeloma: factors related to the tumor and factors related to T-cells, and further discusses the importance of using new tools and technologies to better understand these causes of resistance. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.

Transcript (edited for clarity)

So it was kind of very interesting, because we start by reviewing what are the immunotherapies in myeloma, the IMiDs for example, immunomodulatory drugs and we know have an anti-tumor effect, as well as an effect on all the immune cells present in the bone marrow.

Then we dive in into the T-cell therapies, CAR-T bispecifics. This is where I think we have a lot of expectation because we have seen very promising results and despite that, we have still patients, they progress on it...

So it was kind of very interesting, because we start by reviewing what are the immunotherapies in myeloma, the IMiDs for example, immunomodulatory drugs and we know have an anti-tumor effect, as well as an effect on all the immune cells present in the bone marrow.

Then we dive in into the T-cell therapies, CAR-T bispecifics. This is where I think we have a lot of expectation because we have seen very promising results and despite that, we have still patients, they progress on it. Then I think all are wanting to do more correlative studies to identify what are the predictors of response, the cause of resistance, that from my point of view, they are mostly coming from two major factors, can be related to the tumor. We know that myeloma cells, unfortunately, have a way to escape, even the more effective therapy by for example, when they lose BCMA, which is the target of many of these therapies. So unfortunately, that is something you have to keep in mind from our point of view, when we treat the patient.

From the other side, all the T-cell factors, they are important for these new therapies to work. And I’m thinking about CAR-T persistence, I’m talking about T-cell exhaustion that plays a role in resistance. So I think we are learning that we’re really touching just the surface of this mechanism, but we are thinking that with all the new tools, the technology, we can answer and understand a bit more about the cause of resistance in our patient.

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