A large, real-world study has affirmed the effectiveness of axicabtagene ciloleucel (axi-cel) in treating relapsed or refractory (r/r) large B-cell lymphoma (LBCL), even in patients who would have been ineligible for the pivotal ZUMA-1 trial. The study, which included 1297 patients from 78 centers, demonstrated that axi-cel maintained a comparable efficacy profile in a broader patient population, suggesting that eligibility criteria for CAR-T therapy could be expanded.
Key Findings on Efficacy
At a median follow-up of 12.9 months, the overall response rate (ORR) was 73%, with a complete response (CR) rate of 56%. Median overall survival (OS) was 21.8 months (95% CI, 17.4-28.8), and median progression-free survival (PFS) was 8.6 months (95% CI, 6.5-12.1). Notably, the duration of response (DOR) for ZUMA-1 ineligible patients was similar to that of the ZUMA-1 eligible group, indicating that comorbidities did not significantly impede the treatment's effectiveness. Multivariable analysis showed that ECOG performance score ≥ 2 and chemoresistance prior to infusion were associated with inferior outcomes.
Safety Profile and Elderly Patients
The study also evaluated the safety of axi-cel in the real-world setting. While cytokine release syndrome (CRS) occurred in 83% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 55%, rates of grade 3 or higher CRS and ICANS were 8% and 24%, respectively. Interestingly, patients aged 65 years or older had favorable ORRs, despite experiencing higher rates of CRS and ICANS. This suggests that age alone should not be a deterrent to axi-cel treatment.
Implications for Clinical Practice
These findings have significant implications for clinical practice. According to the researchers, patient selection for axi-cel should consider comorbidities and the risk-to-benefit ratio, rather than strictly adhering to ZUMA-1 eligibility. This could potentially expand access to this life-saving therapy for a larger number of patients with r/r LBCL. The study underscores the importance of real-world evidence in validating clinical trial results and informing treatment decisions.
Study Limitations
The authors acknowledged several limitations, including the observational nature of the study, the lack of central review of response assessments, and the absence of data on tumor burden, systemic inflammation, and CAR-T cell expansion. Additionally, characteristics of patients who did not receive axi-cel were not reported, and ZUMA-1 eligibility was not based on intention-to-treat. Despite these limitations, the study provides valuable insights into the real-world use of axi-cel and supports its effectiveness in a broader patient population.
