Comparing Efficacy, Safety, and Pre-Infusion Period of Axicabtagene Ciloleucel vs Tisagenlecleucel in Relapsed/Refractory Large B-Cell Lymphoma.

Abstract Introduction Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are autologous anti-CD19 chimeric antigen receptor T (CAR T) cell therapies for the treatment of patients with relapsed/refractory large B-cell lymphoma (RR-LBCL). Both can induce durable responses; however, cross-trial comparisons are difficult due to differences in study design. In this study, the registration trials of axi-cel and tisa-cel were compared using a matching adjusted indirect comparison (MAIC). Methods A MAIC was performed to adjust for differences in patient characteristics between trials. The estimates for the ZUMA-1 (axi-cel) trial were adjusted using patient-level data to match the study population in JULIET (tisa-cel) for key variables: IPI, ECOG, stage, refractoriness or relapsed disease, double/triple hit status, cell-of-origin, and number of prior lines of therapy. The endpoints analysed were response, overall survival (OS), and adverse events. Results After adjusting for differences in patient characteristics between trials, axi-cel was associated with a greater objective response rate (relative risk [RR] =1.61 [95% CI 1.29-2.01]) and complete response (RR = 1.62 [1.16-2.27]) than tisa-cel among patients who underwent infusion. The OS from infusion onward comparing axi-cel to tisa-cel had a hazard ratio of 0.51 (0.31-0.83). The indirect comparison showed a higher rate of Grade 1-2 cytokine release syndrome (CRS) in ZUMA-1 compared with JULIET; (RR =2.03 [1.55-2.65]) and similar rates of Grade ≥3 CRS and neurologic events (NE). Conclusions In the absence of a direct head-to-head study, the MAIC statistical technique suggests axi-cel may have superior efficacy but a greater risk of Grade 1-2 CRS. Future real world studies can further inform the relative efficacy and safety of CAR T therapies in RR-LBCL.