Non-ICANS and Delayed Neurotoxicity With CAR T: Risk Factors and Ways to Prevent
Panelists discuss emerging strategies to manage delayed neurotoxicity from chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma, highlighting the predictive value of postinfusion lymphocyte expansion, the potential of early dexamethasone intervention, and the need for continued research and collaboration to refine toxicity prevention and ensure safer, broader use of CAR T in earlier treatment lines.
EP: 1.Late-Line R/R: Treatment Landscape
EP: 2.Outcomes and Factors for Consideration When Choosing Between CAR T Therapies
EP: 3.Comparing CAR T Safety, Efficacy in Relapsed/Refractory Multiple Myeloma
EP: 4.Role of Talquetamab as Bridging Therapy for CAR T-Cell Therapy
EP: 5.Optimal Sequencing Strategies for CAR T and Bispecifics in R/R MM
EP: 6.Role of CAR T in Earlier Lines for R/R MM
EP: 7.Non-ICANS and Delayed Neurotoxicity With CAR T: Risk Factors and Ways to Prevent
EP: 8.Real-World Data of SOC Cilta-Cel in R/R MM and Cilta-Cel in Patients With High-Risk Features
EP: 9.Identifying and Treating Patients With Adverse Prognostic Factors
EP: 10.Supportive Care: Infection Disease Prophylaxis and Advice for Community Doctors
EP: 11.Best Practices for Referring Patients for CAR T Therapy
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.
