(CSPOT41) Effectiveness of Axicabtagene Ciloleucel versus Conventional Treatments as First-line Therapy in Patients With High-risk Large B-cell Lymphoma: a Retrospective External Comparator Study

Background: Axicabtagene ciloleucel (Axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory diffuse large B-cell lymphoma. Recent findings from ZUMA-12 single-arm trial have further elucidated its therapeutic potential as a frontline regimen for high-risk large B-cell lymphoma (LBCL), yet there is a paucity of data on head-to-head comparison between axi-cel vs conventional therapy in improving patient survival.

Objectives: To explore overall survival (OS) and progression-free survival (PFS) associated with axi-cel in patients with high-risk LBCL

Methods: We conducted external comparator arm study, comparing treatment outcomes in patients treated with axi-cel from ZUMA-12 (NCT03761056) with external comparator arm (ECA) treated with conventional therapy from SMC-LCS (Samsung Medical Center-Lymphoma Cohort Study; NCT03117036); published summary data from ZUMA-12 and individual patient data from SMC-LCS were used. Patients enrolled in SMC-LCS between 2017 and 2023 were included in the ECA after fulfilling the key eligibility criteria of ZUMA-12: double- or triple-hit lymphoma (MYC, BCL2, or BCL6 translocations) or LBCL and an International Prognostic Index (IPI) 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 ratio (aHR) with 95% confidence interval (CI), comparing ZUMA-12 vs ECA, were estimated using Cox proportional hazards model.

Results: Of 279 patients with high-risk LBCL in SMC-LCS, 45 fulfilled ZUMA-12 eligibility criteria. Substantial imbalances in the baseline characteristics between ZUMA-12 and ECA were resolved after applying MAIC. By the end of study, all-cause mortality rates were 13.5% for ZUMA-12 and 49.5% for weighted ECA, corresponding to a lower hazard of death for axi-cel with aHR of 0.30 (95% CI 0.13-0.73). Median PFS of ZUMA-12 was not reached vs 2.7 months in the weighted ECA, corresponding to improved PFS for axi-cel with aHR of 0.23 (95% CI 0.11-0.46).

Conclusions: In 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.