CAR T Safety in Practice: Clinical Approaches to Early and Late Toxicity Management

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated strong efficacy in treating lymphoma, particularly when standard chemotherapy has failed. However, these therapies are not without adverse effects, with cytokine release syndrome (CRS) being one of the most common and earliest toxicities, often appearing within the first few days after infusion. CRS is driven by the activation of T cells and subsequent systemic inflammation. Fortunately, supportive measures such as tocilizumab and corticosteroids have been effective in managing symptoms without compromising efficacy. In high-risk patients—those with elevated lactate dehydrogenase or significant tumor burden—prophylactic corticosteroids, as outlined in the FDA-approved label, have helped reduce the incidence of severe CRS, making the treatment safer even for older or more frail individuals.

Neurotoxicity, or immune effector cell–associated neurotoxicity syndrome (ICANS), has also been a concern with CAR T, particularly with axicabtagene ciloleucel (axi-cel). However, with improved monitoring and earlier intervention protocols, the frequency and severity of ICANS have decreased significantly over time. High-grade neurotoxicity now occurs in approximately 12% to 15% of cases, a marked improvement from earlier reports. While these rates remain somewhat higher than those associated with liso-cel, the tolerability of both agents has improved due to better management strategies.

In clinical decision-making, product selection often comes down to patient-specific factors. In the case of a patient with primary refractory disease, axi-cel may be preferred due to its demonstrated overall survival benefit and more reliable, rapid manufacturing timeline—often within 2 weeks. This allows clinicians to initiate treatment quickly, which can be crucial in aggressive disease settings. While lisocabtagene maraleucel (liso-cel) may still be appropriate, particularly for patients with lower toxicity thresholds, the urgency and aggressiveness of the disease often tilt the balance in favor of axi-cel in such scenarios.