Pod24 and cr30 are promising surrogate endpoints for assessing the outcome of patients with advanced stage follicular lymphoma enrolled in the foll05 trial by fil.

Introduction: In an indolent disease like Follicular lymphoma (FL), the availability of validated and accurate early surrogates of survival would allow a faster assessment of treatment efficacy. Recently, the progression of disease within 24 months after diagnosis (POD24) and the lack of complete remission within 30 months after diagnosis (CR30) were suggested as promising early endpoints as they were both highly predictive of survival. We investigated the role of POD24 and of CR30 in our series of patients with advanced stage FL prospectively enrolled in the FOLL05 trial (NCT00774826). The aim of this analysis was to validate the main study results with POD24 and CR30 and to further assess their impact on patients' outcome. Methods: From March 2006 to September 2010, 534 patients were enrolled into the FOLL05 trial, by 58 Italian Institutions. Patients were randomized among R-CVP, R-CHOP or R-FM. POD24 and CR30 were correlated with Progression free survival (PFS) and Overall Survival (OS). CR30 was calculated according to original method (Qian Shi et al. JCO, 2017). To align the endpoints, POD24 and CR30 are labeled as fail (F) for progression within 24 months, no CR30 and achieve (A) for no POD24 and achieve CR30, respectively. Results: Median follow-up was 84 months (range 1–119). One hundred and forty-one patients (28%) failed POD24, and 235 (47%) failed the CR30 endpoint. Five-year OS was 79% and 95% for patients failing and achieving POD24 (p < 0.001) and was 82% and 98% for patients failing to achieve and achieving CR30 (p < 0.001). Prognostic role of POD24 and CR30 was observed for all three study arms (p < 0.001). Both indexes retained their prognostic role for OS after adjustment by FLIPI (p < 0.001) and FLIPI2 (p < 0.001). In POD24 analysis, the OR adjusted by FLIPI2 between R-CHOP vs. R-CVP was 0.70 (95%CI 0.43–1.13, p = 0.148) and 0.58 (95%CI 0.36–0.94, p = 0.027) between R-FM vs. R-CVP. In CR30, the OR adjusted by FLIPI2 between R-CHOP vs. R-CVP was 0.63 (95%CI 0.40-0.98, p = 0.043) and 0.57 (95%CI 0.36–0.89, p = 0.013) between R-FM vs. R-CVP. Five-year OS was 95% for patients achieving both POD24 and CR30 (267; 53%), 86% for those failing CR30 (94; 19%) and 74% for patients failing both POD24 and CR30 (141; 28%) (Figure 1. OS stratified by groups obtained combining POD24 with CR30). Keywords: follicular lymphoma (FL).