Validation of POD24 As a Robust Early Clinical Endpoint of Poor Survival in FL from 5,225 Patients on 13 Clinical Trials.

Abstract

Observational studies and standalone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of FL patients in the pre- and post-rituximab era to identify clinical factors predicting POD24. Logistic regression models evaluated the association between clinical factors and POD24. Cox regression evaluated the association between POD24 as a time-dependent factor and subsequent overall survival (OS). A landmark analysis evaluated the association of POD24 on OS for the subset of patients who were alive at 24 months post trial registration. Patients without progression at 24 months at baseline had favorable performance status (PS), limited stage (I/II) disease, low FLIPI risk score, normal baseline hemoglobin, and normal baseline beta 2 microglobulin (B2M). In a multivariable logistic regression model, male gender (odds ratio (OR) = 1.30), PS >= 2 (OR = 1.63), B2M (>= 3mg/L) (OR = 1.43), and high FLIPI risk score (3 - 5) (OR = 3.14) were associated with increased risk of progression before 24 months. In the time-dependent Cox model and the 24 month landmark analysis, POD24 was associated with poor subsequent OS (hazard ratio (HR) = 4.85 and HR = 3.06, respectively). This is the largest pooled analysis using clinical trials data validating POD24 as a robust indicator of poor FL survival and identified clinical predictors of early death and progression that can aid in building comprehensive prognostic models incorporating clinical and molecular predictors of POD24.