Predicting the Early-Phase CAR T Toxicities for B-Cell Lymphomas

Alexandra Lynch explains that CAR T toxicity management has become increasingly algorithmic and predictable based on specific product characteristics. Different CAR T products exhibit distinct cytokine release syndrome (CRS) patterns: Axicabtagene ciloleucel shows rapid CRS onset between days 2 and 4 with quick resolution, lisocabtagene maraleucel demonstrates slower onset around day 5 with gradual resolution, and brexucabtagene autoleucel typically presents around day 3. Understanding these patterns helps health care teams anticipate and prepare for toxicities.

Neurologic toxicity (ICANS) typically follows CRS rather than occurring independently, providing reassurance to patients who fear sudden onset of confusion or speech difficulties. ICANS usually develops in the day 5 to 7 window as CRS begins resolving. Inflammatory markers including C-reactive protein, IL-6, and ferritin can predict impending toxicity, with IL-6 levels often doubling before fever onset, allowing teams to provide anticipatory guidance to patients and families.

Dana-Farber tracks specific inflammatory markers to predict toxicity timing, though Lynch acknowledges this approach varies among institutions. While most patients follow predictable patterns within the expected time frame, outliers with early or late toxicity can occur. Machine learning technologies are being developed to assist newer centers in toxicity prediction, but experience with product-specific patterns remains valuable for established centers managing these complex treatments.