Inside the Clinic: JTCC Experts Highlight Optimal Strategies for CAR T-Cell–Related AEs

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Lori A. Leslie, MD, assistant professor, Hackensack Meridian School of Medicine, director, Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs, John Theurer Cancer Center, and Andre H. Goy, MD, physician in chief of the Hackensack Meridian Health Oncology Care Transformation Services, chairman and chief physician officer at John Theurer Cancer Center at Hackensack University Medical Center, and Lymphoma Division Chief at the John Theurer Cancer Center, discuss optimal strategies for CAR T-cell–related adverse effects (AEs).

Preemptive strategies with tocilizumab (Actemra) and steroids can help mitigate acute AEs associated with CAR T-cell therapy. Following CAR T-cell therapy infusion, important long-term AEs to be aware of include cytopenias, immunoglobulin (Ig) recovery, immune system recovery, and hypogammaglobulinemia, Goy and Leslie say. Currently, with supportive care, approximately 75% of patients recover their CD4 counts and Ig levels 2 years after infusion. 

Short-term AEs to be aware of are cytokine release syndrome (CRS) and neurotoxicity, Leslie says. Notably, neurotoxicity, which can be a concerning early-onset toxicity, generally resolves completely, Goy says. In early-phase studies with CAR T-cell therapy, intervention was more common in the event of grade 3 CRS or neurotoxicity. Now, earlier intervention strategies are recommended, which has led to milder presentations of these AEs, such as fever and blood pressure changes, Leslie says. Notably, such interventions have not negatively affected efficacy outcomes, Leslie adds. Ultimately, close monitoring during the first period following infusion is necessary, when CRS and neurotoxicity are most common, because neurotoxicity, for example, can present as something as subtle as a change in writing or something as severe as encephalopathy, Leslie concludes.