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EHA 2025 | Absolute lymphocyte count as a predictor of neurotoxicity in patients with RRMM receiving cilta-cel
Yi Lin, MD, PhD, Mayo Clinic in Rochester, MN, discusses predictors of later-onset neurotoxicities in patients with relapsed/refractory multiple myeloma (RRMM) who received ciltacabtagene autoleucel (cilta-cel) in the CARTITUDE studies. The study found that an increase in absolute lymphocyte count is a risk factor, and Dr Lin suggests potential mitigation strategies. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
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Transcript
Yeah, on behalf of my colleague co-investigators from the CARTITUDE studies, we wanted to look at what are some of the predictors associated with later onset toxicities, particularly the neurotoxicities. Now these are uncommon and compared to the late-line therapy study the CARTITUDE-1 to earlier line CARTITUDE-4, CARTITUDE-2, we are seeing a reduction in the frequency of these toxicities occurring just from some of the mitigating strategies, like reducing the myeloma disease burden before we infuse the CAR T-cells...
Yeah, on behalf of my colleague co-investigators from the CARTITUDE studies, we wanted to look at what are some of the predictors associated with later onset toxicities, particularly the neurotoxicities. Now these are uncommon and compared to the late-line therapy study the CARTITUDE-1 to earlier line CARTITUDE-4, CARTITUDE-2, we are seeing a reduction in the frequency of these toxicities occurring just from some of the mitigating strategies, like reducing the myeloma disease burden before we infuse the CAR T-cells. But they’re not at 0%. So we wanted to see what other predictors can we find. And by looking at patients who did develop cranial nerve palsies or Parkinsonism, which typically would happen sometime within that first six months, you know, sometime around months two, three being most common, post-infusion, compared to the patients who didn’t get these side effects. What we found is that after the CAR-T infusion, the patients who had a higher expansion of the lymphocyte count, which also corresponded to higher expansion of the CAR T-cells, are at increased risk. So now, before patients develop the symptoms, we have a way to tell earlier, so these typically happen around the first week two or so, when expansion happens, to say, well, these patients are at some increased risk. And so, you know, are there early mitigation strategies that we can try potentially at that time? So not necessarily for all patients, but only patients who had some of these increased features. So this will be the next thing with the subsequent CARTITUDE studies as a low-hanging fruit, something that could be readily available in the clinic to try would be a very short course of steroids to see if by reducing the expansion of the CAR T-cells at that time, would it help reduce the risk? So hopefully in the coming congresses, we may see some updates related to that.
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