Dr Lee on the Real-World Safety Profile of Axi-Cel in R/R LBCL

“What we found is that the toxicity profile [of axi-cel], including CRS and ICANS, was similar [between the real-world analysis] and the ZUMA-7 trial for the short-term follow-up.”

Dasom (Caroline) Lee, MD, Hematology and Medical Oncology Fellowship Program, Stanford Medicine, Stanford Health Care, details the real-world safety results for the second-line use of the CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory large B-cell lymphoma (LBCL) compared with outcomes for patients treated with axi-cel in the phase 3 ZUMA-7 trial (NCT03391466).

Findings from the real-world analysis, presented at the 2024 ASH Annual Meeting, demonstrated that patients treated in the real-world setting experienced an objective response rate of 79% and a complete response rate of 64% at a median follow-up of 12.0 months (95% CI, 11.5-12.1). In the real-world study, the 12-month event-free survival rate was 53% (95% CI, 48%-58%), and the 12-month overall survival rate was 71% (95% CI, 56%-76%).

Regarding safety, reports of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were similar at the short-term follow-up between patients in the real-world analysis and the ZUMA-7 trial, Lee begins. Following these data, she notes that a longer-term follow-up will be needed to confirm these findings.

Of note, any-grade CRS following treatment with axi-cel occurred in 87% of patients in the real-world analysis; grade 3 or higher CRS was reported in 5% of patients. Any grade ICANS occurred in 50% of patients, and grade 3 or higher ICANS occurred in 22%.

More non-relapse mortalities occur at 6 months in patients who were ineligible for the ZUMA-7 trial, Lee explains. Major factors causing ineligibility included organ impairment (34%) and prior malignancies (16%). Therefore, she emphasizes the importance of having a long-term follow-up to not only help confirm the findings from the real-world analysis but also to identify the drivers of non-relapse mortality. After this is established, the next step is to prevent these complications for the respective patient population, Lee concludes.