PB1782 TWO‐YEAR SURVIVAL WITH AXICABTAGENE CILOLEUCEL IN RELAPSED OR REFRACTORY LARGE B‐CELL LYMPHOMA: AN UPDATED ANALYSIS

Abstract

Background:Relapsed/refractory large B cell lymphoma is historically associated with a poor prognosis, with a median overall survival (OS) of 6.3 months. In the 2‐year update of the ZUMA‐1 trial of axicabtagene ciloleucel (axi‐cel), median OS was not reached after a median follow‐up of 27.1 months. Prior analysis at 1‐year suggests that traditional parametric survival models cannot accurately estimate long‐term OS with axi‐cel when a large proportion of patients achieve durable remissions, thereby supporting the use of a mixture cure model (MCM) for survival extrapolations (Bansal, et al. Biol Blood Marrow Transplant. 2018).Aims:We analyzed the updated 2‐year ZUMA‐1 data to further explore the robustness of MCM.Methods:The ZUMA‐1 data were analyzed using a traditional parametric model, MCM, a general mixture model (GMM), and an integrated Markov cure model (IMCM). The MCM assumed patients with long‐term OS would have similar mortality as the age‐adjusted general population. The GMM relaxed this assumption by separately fitting and then combining parametric survival functions for poor‐ and good‐prognosis patients in a single survival function. The IMCM simultaneously accounted for OS and disease progression in a single framework. All parameters were estimated via maximum likelihood estimations, and model fit was assessed via Akaike information criterion (AIC).Results:The best‐fitting traditional model estimated a mean OS of 10.6 years (AIC = 444.3). The best‐fitting MCM estimated a mean OS of 13.5 years, with a 51.0% long‐term OS fraction (AIC = 439.3). The best‐fitting GMM produced a mean OS of 13.5 years, with a 52.7% long‐term OS fraction (AIC = 442.1). The best‐fitting IMCM estimated a mean OS of 13.4 years, with a 50.5% long‐term OS fraction (AIC = 916.6). The higher AIC for GMM and IMCM is partly because of specifying more parameters than MCM.Summary/Conclusion:Analyzing the updated ZUMA‐1 2‐year data, both the GMM and IMCM showed good model fit and results consistent with those of the MCM. These results support the long‐term survival associated with axi‐cel in relapsed/refractory large B cell lymphoma driven by the ≥ 50% long‐term OS rates.