Efficacy of Axicabtagene Ciloleucel Compared to Historical Treatments for Relapsed/Refractory Diffuse Large B-cell Lymphoma of Asian Descent: A Matching Adjusted Indirect Comparison of ZUMA-1 vs REAL-TREND

Background : To better understand the comparative effectiveness of axicabtagene ciloleucel (axi-cel) to historical standard of care (SoC) for the treatment of refractory diffused large B-cell lymphoma (DLBCL) among patients of Asian descent, we conducted a matching-adjusted indirect treatment comparison (MAIC) of the pivotal ZUMA-1 trial (NCT02348216 registered in 2015) and the Asia-based REAL-TREND cohort. Methods : The individual patient data (IPD) from ZUMA-1 (n = 101 infused patients) used the 60-month data-cut, while the REAL-TREND cohort data consisted of aggregate data and pseudo-IPD derived from digitized curves using the Guyot algorithm. The outcomes assessed were overall survival (OS), complete response (CR) and overall response rate (ORR), as reported in REAL-TREND. The MAIC weights were derived using age ≥60, sex, proportion of fourth line or higher (4L+) patients, international prognostic index (IPI; 0-1 vs 2 vs 3 vs 4-5), and refractory to SCT. Sensitivity analyses explored the use of the intention to treat population, alternative variable alignment and use of central review assessed response outcomes for ZUMA-1. Results : Somebaseline characteristics were similar across ZUMA-1 and REAL-TREND, such as age and IPI scores, but key differences included proportion of 4L+ patients (69% vs 9%), of ECOG performance score 0-1 (100% vs. 59%), and type of refractoriness. The MAIC models aligned on prior lines and refractoriness, while differences in ECOG performance scores were captured through IPI. The resulting effective sample size for ZUMA-1 was 31.1. The estimated hazard ratio for OS was 0.27 (95% confidence interval [CI]: 0.15-0.50) and sensitivity analyses led to similar estimates. Strong effects were estimated for both ORR (odds ratio: 20.76; 95% CI: 7.18-60.02) and CR (odds ratio: 15.25; 95% CI: 6.84-33.98). Conclusion : The comparative efficacy of axi-cel relative to historical SoC was similar to that observed in studies restricted to Western settings. By providing outcomes data within a population of Asian-descent, we can provide better economic modeling to support reimbursements and improved access.