Axicabtagene ciloleucel (axi-cel; Yescarta) continues to demonstrate its efficacy as a second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL) in real-world settings, mirroring the outcomes observed in the pivotal ZUMA-7 trial. The recent analysis, presented at the 2024 ASH Annual Meeting, provides crucial insights into the treatment's effectiveness and safety in a more diverse patient population than typically enrolled in clinical trials.
The study, led by Dr. Dasom (Caroline) Lee from Stanford University, included 446 patients with relapsed/refractory LBCL. A significant 52% of these patients would have been ineligible for the ZUMA-7 trial, primarily due to organ impairment (34%) and prior malignancies (16%). Despite this, the real-world data showed an objective response rate (ORR) of 79% and a complete response rate of 64% at a median follow-up of 12 months. The 12-month event-free survival (EFS) rate was 53% (95% CI, 48%-58%), and the 12-month overall survival (OS) rate was 71% (95% CI, 56%-76%).
Efficacy Parallels ZUMA-7
The effectiveness of axi-cel in the real-world study closely aligned with the results from the ZUMA-7 trial. "We demonstrated similar effectiveness with axi-cel compared with data from ZUMA-7, including for EFS and OS," Dr. Lee noted. This consistency is particularly encouraging, as it suggests that the benefits of axi-cel extend beyond the highly controlled environment of a clinical trial to a broader range of patients encountered in routine clinical practice.
Safety Profile Consistent
The safety profile of axi-cel in the real-world analysis was also consistent with the ZUMA-7 trial. Any-grade cytokine release syndrome (CRS) occurred in 87% of patients, with grade 3 or higher CRS reported in only 5%. The rates of any-grade and grade 3 or higher immune effector cell–associated neurotoxicity syndrome (ICANS) were 50% and 22%, respectively. Dr. Lee mentioned that longer follow-up is needed to confirm these findings and to investigate the causes of non-relapse mortality observed in patients ineligible for ZUMA-7.
Implications for Clinical Practice
These real-world data have significant implications for patient selection and treatment strategies. The study suggests that axi-cel can be effectively used in a broader clinical setting, including patients with comorbidities and prior malignancies who may have been excluded from the ZUMA-7 trial. However, Dr. Lee emphasized the importance of risk stratification in these patients, given the higher incidence of non-relapse mortality observed in the ZUMA-7 ineligible group. Further analysis with long-term follow-up is needed to better understand the factors driving this increased mortality and to develop strategies for prevention.
The FDA approved axi-cel for second-line treatment of LBCL in April 2022, based on the ZUMA-7 trial results. This real-world evidence reinforces the value of axi-cel as a second-line option for patients with relapsed or refractory LBCL, offering hope for improved outcomes even in those with complex medical histories.
