OBJECTIVES: Axi-cel and tisa-cel are approved, autologous anti-CD19 CAR T cell therapies for the treatment of patients (pts) with RR-LBCL. Both can induce durable responses; however, cross-trial comparisons are difficult due to differences in study design, patient population, bridging chemotherapy allowance, and time from leukapheresis to treatment. 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 pt characteristics between trials. The estimates for the ZUMA-1 (axi-cel) trial were adjusted using pt-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 impact of leukapheresis to infusion time was modeled using published data (Crump, 2017). The endpoints analyzed were response, overall survival (OS), and adverse events.

RESULTS: After adjusting for differences in pt characteristics between trials, axi-cel was associated with a greater objective response rate (relative risk [RR] =1.62 [95% CI 1.28-2.06]) and complete response (RR = 1.56 [1.10-2.20]) than tisa-cel among pts who underwent infusion. The OS from leukapheresis onward comparing axi-cel to tisa-cel had a hazard ratio of 0.43 (0.28 – 0.63). The mean survival for the 24-mo follow-up period from leukapheresis showed a difference of 6.3 mo (4.2 – 8.5) favoring axi-cel. The indirect comparison showed a higher rate of Grade 1-2 cytokine release syndrome (CRS) in ZUMA-1 compared with JULIET; (RR = 2.02 [1.55-2.65]), and similar rates of Grade ≥3 CRS, Grade 1-2 neurologic events (NE), and Grade ≥3 NE.

CONCLUSIONS: Given available evidence limitation, this indirect comparison suggests axi-cel may have superior efficacy but a greater risk of Grade 1-2 CRS. Future studies are needed to confirm the relative efficacy and safety of CAR T therapies in RR-LBCL.