Matching‐adjusted indirect comparison of axicabtagene ciloleucel versus mosunetuzumab in relapsed/refractory follicular lymphoma patients after 2 prior systemic treatments

Introduction: Follicular lymphoma (FL) is an indolent form of non-Hodgkin’s lymphoma; however, relapsed/refractory (R/R) FL patients tend to have poor outcomes. Axicabtagene ciloleucel (axi-cel) was the first chimeric antigen receptor (CAR) T-cell therapy approved for R/R FL patients. More recently, mosunetuzumab was the first bispecific monoclonal antibody approved in R/R FL. We sought to conduct a matching-adjusted indirect comparison (MAIC) to estimate the comparative efficacy and safety of axi-cel and mosunetuzumab for the treatment of 3rd line or higher (3L+) FL. Methods: The evidence base consisted of individual patient data (IPD) from the single-arm axi-cel trial, ZUMA-5, and publications identified through a systematic review pertaining to the mosunetuzumab trial (NCT02500407). For each outcome, prognostic factors—including progression within 24 months of frontline initiation (POD24), refractory status, double refractory, prior stem cell transplant—were a priori identified through quantitative analysis and clinical experts. Outcomes were progression-free survival (PFS), duration of response (DoR), objective response rate (ORR), complete response rate (CRR), and safety. Analyses used independent central review for both trials, where possible. Overall survival (OS) was not analyzed as mosunetuzumab data were immature and not reported in the latest publication. As IPD for axi-cel and aggregate data for mosunetuzumab were available, unanchored MAICs were conducted to align ZUMA-5 to the patient characteristics of the mosunetuzumab trial. Hazard ratios (HRs) from Cox regression were used to compare time-to-event outcomes using pseudo-IPD extracted from published Kaplan-Meier plots for mosunetuzumab and the remaining outcomes were compared using odds ratios (ORs). Index date for ZUMA-5 was date of leukapheresis and included all enrolled patients. Results: Patient characteristics were generally well-aligned between trials leading to large effective-sample sizes after matching, ranging from 99.2 to 109.9, for ZUMA-5 (n = 127). In comparisons to mosunetuzumab (n = 90), axi-cel was associated with improved PFS (HR: 0.38; 95% confidence interval [CI]: 0.23–0.61) and DoR (HR: 0.45; 95% CI: 0.26–0.77). Results were consistent for response outcomes (Figure 1). Sensitivity analyses led to similar results. Although axi-cel was associated with a higher rate of all-grade cytokine release syndrome (CRS) and neurological events (NE), differences in Grade ≥3 (G3+) CRS and treatment-related adverse events (TRAEs) were not statistically significant. Differences in G3+ NE were not evaluable. The research was funded by: Kite, A Gilead Company Keywords: Cellular therapies, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. M. D. Ray Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite S. Kanters Employment or leadership position: RainCity Analytics Research funding: RainCity Analytics S. Beygi Employment or leadership position: Gilead/Kite Research funding: Gilead/Kite T. Best Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite J. Wulff Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite E. H. Limbrick-Oldfield Employment or leadership position: RainCity Analytics A. R. Patel Employment or leadership position: Gilead/Kite Stock ownership: Gilead/Kite O. O. Oluwole Consultant or advisory role: Pfizer, Gilead/Kite, AbbVie, Janssen, TGR Therapeutics, ADC, Novartis, Epizyme, Curio Science, Nektar, Syncopation Honoraria: Pfizer, Gilead