Non-ICANS and Delayed Neurotoxicity With CAR T: Risk Factors and Ways to Prevent

EP: 1.Late-Line R/R: Treatment Landscape

EP: 2.Outcomes and Factors for Consideration When Choosing Between CAR T Therapies

EP: 3.Role of Talquetamab as Bridging Therapy for CAR T-Cell Therapy

EP: 4.Optimal Sequencing Strategies for CAR T and Bispecifics in R/R MM

EP: 5.Role of CAR T in Earlier Lines for R/R MM

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EP: 6.Non-ICANS and Delayed Neurotoxicity With CAR T: Risk Factors and Ways to Prevent

Managing neurotoxicity, particularly the delayed non–immune effector cell–associated neurotoxicity syndrome events associated with CAR T-cell therapy, is a growing focus in optimizing treatment for multiple myeloma. Risk factors such as high disease burden at the time of infusion have been linked to increased toxicity, highlighting the importance of effective disease control and cytoreduction beforehand. Notably, new findings suggest that a rapid expansion of absolute lymphocyte count (ALC) post infusion may predict neurotoxic complications, such as parkinsonism or cranial nerve palsies. Encouragingly, early intervention using dexamethasone to manage ALC levels appears to reduce this risk, providing a simple and practical strategy in clinical settings.

Although dexamethasone is promising, questions remain about its long-term safety and the need for more targeted interventions. The risk of infections—already a significant contributor to nonrelapse mortality in CAR T recipients—necessitates additional measures, such as prophylactic intravenous immunoglobulin, to support immune function during this vulnerable period. In extreme cases of uncontrolled lymphocyte proliferation, chemotherapy agents like cyclophosphamide have been used successfully to temper expansion. These interventions are still under study, and more data are needed to establish standardized protocols. Beyond ALC, researchers are also exploring direct CAR T-cell quantification by flow cytometry, though ALC remains a useful surrogate in the early weeks after lymphodepletion.

Ultimately, understanding and preventing delayed neurotoxicity is key to safely expanding CAR T access, especially in earlier lines of therapy. Collaborative multicenter efforts are critical for identifying predictive biomarkers and refining interventions. As with earlier challenges in myeloma care—like bortezomib-related neuropathy—these toxicities can become manageable with experience and innovation. Continued vigilance, patient selection, and proactive toxicity management will help maximize the benefit of this powerful treatment while minimizing its risks.