Effectiveness of axicabtagene ciloleucel versus conventional treatments as first-line therapy for high-risk large B-cell lymphoma: an external comparator study.

backgroundEfficacy of Axicabtagene ciloleucel (Axi-cel) as a frontline regimen for high-risk large B-cell lymphoma (LBCL) has been described in ZUMA-12 single-arm trial, yet there is a paucity of data on head-to-head effectiveness comparison between axi-cel vs. conventional therapy.

methodsWe conducted an external comparator arm study to compare overall survival (OS) and progression-free survival (PFS) in patients treated with axi-cel from ZUMA-12 with external comparator arm treated with conventional therapies from SMC-LCS (Samsung Medical Center-Lymphoma Cohort Study 2017-2023); published summary data from ZUMA-12 and individual patient data from SMC-LCS were used. Patients from SMC-LCS fulfilling the key eligibility criteria of ZUMA-12 were included: double- or triple-hit lymphoma (MYC, BCL2, or BCL6 translocations) or LBCL and an International Prognostic Index score of ≥ 3. OS was defined as a time interval between initiation of the index treatment and date of all-cause death or last follow-up visit. PFS was defined as a time interval between initiation of the index treatment and occurrence of the events related to disease progression or all-cause death. Kaplan-Meier curves for OS and PFS in the ZUMA-12 were extracted using Engauge Digitizer software (Version 12.1). Propensity score weighting using matching-adjusted indirect comparison (MAIC) approach was used to compare OS and PFS, adjusting for the baseline characteristics. The adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards model.

resultsOf 279 patients with high-risk LBCL in SMC-LCS, 45 fulfilled ZUMA-12 eligibility criteria. By the end of study, all-cause mortality rates were 13.5% for axi-cel and 49.5% for weighted external comparator arm, corresponding to a lower hazard of death for axi-cel with aHR of 0.30 (95% CI 0.13-0.73). Median PFS of axi-cel arm was not reached vs. 2.7 months in the weighted external comparator arm, corresponding to improved PFS for axi-cel with aHR of 0.23 (95% CI 0.11-0.46).

conclusionsIn the present study, we leveraged real-world data as a source for external comparator to present clinically meaningful evidence on the comparative effectiveness of axi-cel for treatment of high-risk LBCL.