Dr Leslie on the Management of CAR T-Cell Therapy Toxicities in LBCL

Lori A. Leslie, MD, director, Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs, John Theurer Cancer Center, assistant professor, Hackensack Meridian School of Medicine, discusses the evolution in managing serious toxicities associated with CAR T-cell therapy, specifically cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) in patients with high-risk, relapsed/refractory large B-cell lymphoma (LBCL).

Leslie explains that historically, in studies such as the phase 1/2 ZUMA-1 trial (NCT02348216), which investigated axicabtagene ciloleucel (axi-cel; Yescarta) in patients with refractory LBCL, interventions such as tocilizumab (Actemra) and corticosteroids were delayed until patients exhibited significant toxicity due to concerns about potential efficacy impairment. However, extensive clinical experience has led to a paradigm shift, she says. Early intervention at grade 1 toxicity is now considered safe and does not compromise CAR T-cell therapy efficacy, Leslie notes.

This updated approach allows for earlier management of toxicities, potentially benefiting patients with limited physiological reserves, she continues. Consequently, patients previously deemed ineligible due to concerns about toxicity management may now be considered suitable candidates for CAR T-cell therapy, Leslie explains.

Leslie emphasizes the importance of timely evaluation for CAR T-cell therapy eligibility. Referring physicians often discover that patients previously thought unsuitable may be able to tolerate and benefit from this therapy. The single-infusion treatment offers the prospect of long-term remission without the need for continuous therapy, providing a promising option for eligible patients, Leslie explains.

The refinement of toxicity management strategies in CAR T-cell therapy has expanded the pool of eligible patients by allowing for earlier intervention at lower toxicity grades. This evolution underscores the significance of timely evaluation for CAR T-cell therapy eligibility, potentially benefiting patients with varying levels of physiological reserve, Leslie concludes.