Dr Oluwole on the Importance of Assessing the Onset and Incidence of Axi-Cel–Related Neurotoxicity in R/R DLBCL

"Now that we’ve done a lot of [CAR T-cell therapy infusions], we asked: Is it truly what we thought that most of the AEs will happen and resolve quickly, or do [patients] still have [a high] risk [of developing these AEs] going far out to 28 days? [We wanted to evaluate this] among the patients we have treated."

Olalekan O. Oluwole, MD, MPH, an associate professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center, shared the rationale for evaluating the incidence and timing of adverse effects (AEs) associated with the CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory large B-cell lymphoma (LBCL).

Although CAR T-cell therapy is a one-time infusion, it leads to robust immune activation marked by inflammatory cytokine release, which drives both efficacy and early toxicity, Oluwole began. He explained that axi-cel acts immediately upon infusion, and early AEs are expected due to the therapy’s mechanism of action.

Despite these expectations, current FDA guidelines require monitoring for approximately 28 days post-infusion near the treatment center, Oluwole noted. Given increased clinical experience with CAR T-cell therapies, his group aimed to determine whether the risk of AEs truly extends over the full 28-day period or is primarily confined to the early post-infusion window, he said.

During the 2025 Transplantation and Cellular Therapy Meetings, Oluwole and colleagues presented results from a retrospective analysis of the rates and duration of cytokine release syndrome (CRS) and other neurologic toxicities associated with axi-cel among patients enrolled in the pivotal phase 3 ZUMA-7 trial (NCT03391466) and the phase 2 ZUMA-1 trial (NCT02348216). By day 14, approximately 53% of patients in the ZUMA-7 cohort had achieved durable resolution of CRS and neurologic AEs, defined as resolution lasting 3 or more consecutive days. Although some patients continued to recover from previously experienced AEs, most symptoms had resolved by day 14, supporting a potentially shorter period of intensive monitoring than currently mandated.