Olalekan Oluwole, MD, MPH, is an associate professor of medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center.

  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.

2025 Transplantation and Cellular Therapy Meetings

, Oluwole and colleagues presented results from 

 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.

Videos

Olalekan O. Oluwole, MD, MPH, discusses how AE assessment could guide post-infusion monitoring periods and outpatient axi-cel administration in LBCL.

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

Olalekan O. Oluwole, MD, MPH, details the importance of early intervention regarding adverse effects following CAR T products in relapsed/refractory LBCL. 

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.

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 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.

Olalekan O. Oluwole, MD

"This opens the door for some select patients [to undergo less monitoring for CRS and neurologic toxicities]. Perhaps it might be a reasonable option not to monitor them at the academic center; maybe they can go back home early. Maybe we can use more telemedicine and other means to allow them to get some semblance of a return to normal.”

Olalekan Oluwole, MD, MPH, associate professor of medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, discusses findings from a study on the incidence and resolution of cytokine release syndrome (CRS) and neurological toxicities beyond 2 weeks following the infusion of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory large B-cell lymphoma (LBCL). These data were presented at the 

The analysis evaluated the trajectory of CRS and neurological adverse effects (AEs), which are known toxicities associated with CAR T-cell therapy and require management/mitigation strategies, including staying in proximity of the infusion center for 4 weeks following CAR T-cell therapy infusion.

Findings from the study showed that more than half of patients experienced CRS or neurotoxicities; however, most of these events occurred and resolved within the first 2 weeks post-infusion, Oluwole says. Notably, beyond two weeks post-infusion, Oluwole notes no new instances of CRS or neurological toxicities were reported, and although some patients were still recovering from an AE occurring in the first 2 weeks, most patients experienced full resolution by 2 weeks.

These findings suggest that prolonged hospitalization or extended monitoring at an academic center may not be necessary for all patients with LBCL receiving axi-cel Oluwole notes. Given the requirement for patients to remain within close proximity to their treating centers post-infusion with a caretaker, these data highlight a potential opportunity to modify current post–CAR T-cell monitoring protocols, he explains. Many patients, including those who are employed or reside in rural areas, are required to relocate temporarily for treatment, posing logistical and financial challenges, he continues With the observed low incidence of new-onset toxicities beyond 2 weeks, there is a rationale for exploring alternative monitoring strategies, such as telemedicine, to facilitate earlier patient discharge and allow select patients to return home sooner, Oluwole concludes.

Olalekan Oluwole, MD, MPH, discusses the incidence and resolution of CRS and neurological events beyond two weeks following axi-cel infusion in relapsed/refractory LBCL.

Olalekan O. Oluwole, MD, MPH

Articles

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

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

Dr Oluwole on CRS and Neurotoxicity Beyond 2 Weeks After Axi-Cel Infusion in R/R LBCL