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IMS 2026 | Predicting and monitoring CAR T-cell toxicities in multiple myeloma
Doris Hansen, MD, Moffitt Cancer Center, Tampa, FL, discusses biomarkers that may help predict and monitor toxicities associated with CAR T-cell therapy. She highlights the potential roles of absolute lymphocyte count, CD4-positive T-cell populations, CAR T-cell expansion and inflammatory markers, as well as the SCOPE-MM prognostic model and bridging therapy, in identifying patients at higher risk of immune toxicities and informing supportive strategies. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.
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Transcript
There are novel prognostic models to help us personalize care for our patients because we do need to identify who are the patients that might be a greater source for toxicity and how can we best support them through immunotherapies. One of these models is known as the SCOPE-MM, which is stratification of CAR-T outcomes at pre-apheresis evaluation. Patients who have a high risk are more likely to experience immune toxicities compared to those who are low risk and also infections and non-relapse mortality...
There are novel prognostic models to help us personalize care for our patients because we do need to identify who are the patients that might be a greater source for toxicity and how can we best support them through immunotherapies. One of these models is known as the SCOPE-MM, which is stratification of CAR-T outcomes at pre-apheresis evaluation. Patients who have a high risk are more likely to experience immune toxicities compared to those who are low risk and also infections and non-relapse mortality. An additional point that I make in my talk is about bridging therapy. We do know that bridging therapy is critical in terms of disease response, enhancing that effector-to-target ratio to enhance efficacy and mitigate immune toxicities and non-relapse mortality. In terms of biomarkers across CARTITUDE studies we have seen some important biomarkers for neurotoxicity has been absolute lymphocyte count as well as CD4 positive T cells as well as maximum CAR-T expansion but certainly a more pronounced inflammatory phenotype, whether it be cytokines, regulatory T cells, and a higher neutrophil to leukocyte ratio is also associated with development of Parkinsonism or cranial nerve palsies. And so an ALC, what we’ve seen across studies, an ALC of 3,000 versus less than 3,000 associates with a 13-fold risk of increased neurotoxicity or toxicity and non-response to bridging about 10-fold. Now, lastly, some very elegant studies have shown that these neurotoxicities predominantly associate with CD4-positive central memory T-cells, or naive, as opposed to terminally differentiated T-cells. This is the case across neurotoxicities, colitis. Importantly, the IC enterocolitis, an emerging entity that we’ve seen with siltuximab mostly, and it appears that it occurs without ALC expansion, though it does overlap with patients developing neurotoxicities. So certainly these two might be overlapping, but they’re biologically distinct entities. Lastly, I do think that the future is very much biomarker-driven, and that is to predict and also to prevent toxicities without compromising the great efficacy that we see with our novel immunotherapeutics.
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