Dr Oluwole on AE Mitigation Following Axi-Cel in R/R LBCL

“Approved CAR T[-cell therapies] are autologous and [include] mature T cells. They control the immune system and talk to the other cells of the immune system—monocytes and macrophages. [This] in unison is what causes all of these [adverse] effects.”

Olalekan O. Oluwole, MD, MPH, an associate professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center, detailed strategies for the mitigation 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).

Currently, FDA-approved CAR T-cell therapies are autologous and include mature T cells, Oluwole began. The CAR T cells communicate with other cells within the immune system, such as monocytes and macrophages, and this can lead to AEs, he explained. Although prevention may be impossible, early intervention could help mitigate AEs such as cytokine release syndrome (CRS), specifically by utilizing tocilizumab (Actemra), he said. Of note, he emphasized that tocilizumab helps reduce CRS without affecting the efficacy of the CAR T-cell therapy.

At the 2025 Transplantation & Cellular Therapy Meetings, Oluwole presented data from a retrospective analysis on the incidence and resolution of CRS and neurological toxicities beyond 2 weeks after patients with relapsed/refractory LBCL received an infusion of axi-cel. The study demonstrated that more than half of patients experienced CRS or neurotoxicities occurring within the first 2 weeks following axi-cel infusion. However, findings revealed that no new occurrences of AEs were seen in patients 2 weeks after infusion, although some patients continued recovering from AEs experienced within the first 2 weeks, and most had resolved by the 2-week mark. Specifically, the analysis assessed the trajectory of CRS and neurological AEs, along with the need for daily monitoring at the infusion center for 7 days and remaining close to a certified health care facility for at least 4 weeks after infusion.

Based on known data and experience with CAR T-cell therapies, it has been established that earlier intervention has reduced and shortened toxicity, especially after the first 2 weeks of infusion, Oluwole concluded.