IMS 2025 | Association between CAR-T expansion and delayed neurotoxicity following cilta-cel in myeloma

CAR T-cell therapy has revolutionized patient care with multiple myeloma in the relapse refractory setting. However, it comes with significant toxicities and one of the most concerning toxicities is called delayed neurotoxicity that can happen weeks to months after CAR T-cell infusion. And patients present as cranial nerve palsy, peripheral neuropathy, and in the worst case, it can present as Parkinsonism-like syndrome, which may not be reversible in some cases. And so my study focused on looking at the association between delayed neurotoxicity and CAR-T expansion, as well as absolute lymphocyte count, which can be a surrogate marker for CAR-T, and looking at the association between those two things. We found that the CAR-T expansion or the ALC peak level is not significantly associated with clinical efficacy, but it was strongly associated with neurotoxicity, including ICANS as well as delayed neurotoxicity. And so we also looked at the longitudinal dynamics of lymphocyte count, and we saw that the early rise of the ALC expansion was associated with delayed neurotoxicity. So we thought to identify a good threshold where we can identify patients at risk of delayed neurotoxicity. By doing a lot of analysis, we found that as a clinically actionable threshold, we found that the ALC greater than 3,000 or greater than 2,500 with more than twofold daily increase can effectively identify the majority of patients who go on to develop delayed neurotoxicity. So to translate this finding, we are now launching a study looking at prophylactic strategies and how we can mitigate the delayed neurotoxicity in patients with elevated lymphocyte count.

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