IMS 2026 | Immune fitness and reconstitution after CAR T-cell therapy in multiple myeloma

So at IMS 2026, I was very honored to be on a panel of speakers that talks about immune fitness, immune reconstitution, as it relates to all these novel immunotherapies like CAR-T, T-cell engagers. So in the recent years that we’ve had these very transformative therapies coming to practice, we’ve learned more about the biology of how they work and the immune status that might predict those who would respond to treatment or be refractory or potentially be at risk for toxicities. So for one thing we’ve seen with high-dimensional studies, multi-omic studies with single-cell RNA sequencing for transcriptome profiles, for flow cytometry, recognizing that having T-cells that are exhausted prior to the start of treatment is not good for manufacturing of CAR T-cells and also negatively impact response to T cell engagers. On the other hand, having more naive stem central memory-like phenotype can be helpful to generate the more ideal CAR T product or have the response to T cell engager. What we’ve also seen is it goes beyond just the CAR-positive T-cells. We like to see clonal expansions of certain TCR clones, as well as the TCR clones that have more of an effector phenotype at the time of myeloma cell killing and generation of some type of memory response for long-term response. Now, that being said, we’re also recognizing that sometimes, especially as we move to earlier lines of therapies, including high-risk smoldering myeloma phase, where the cells are quite fit, we may have an overexpansion or more than robust activities. So there are some recent studies that identified different transcriptome profiles of CD4 T cells that are associated with some of the delayed toxicities that we’ve seen with CAR T. I think these are all very important for biologic insight to help us really understand potential opportunities to identify patients at risk or to manage some of these side effects. But what we really need is how to translate some of these high dimensional studies into clinical assays that we can readily order at the bedside and in real time to help inform patient decisions. So right now, there are centers that may be using, for example, very simple tests like absolute lymphocyte count that you can get from a blood count to get some idea for CAR T expansion or having just an adequate number of T cells to respond to these T cell redirecting therapies. Hopefully in the years to come, we may be able to take some more of these learnings into clinically actionable tests.

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