BEYOND MAXIMUM GRADE: A NOVEL, LONGITUDINAL TOXICITY OVER TIME (TOXT) ADVERSE EVENT ANALYSIS OF LENALIDOMIDE IN FOLLICULAR LYMPHOMA IN CALGB 50401 (ALLIANCE)

Abstract

Introduction: Chronically administered agents are increasingly used to treat indolent lymphomas. Tables of high grade (gr) adverse events (AEs) do not provide a time profile of AEs by severity and duration or (Figure Presented) describe longer lasting, low gr AEs pertinent to patients (pts) receiving continuous therapies for months to years. We developed a novel approach for AE analysis, the Toxicity over Time (ToxT, Thanarajasingam et al., Lancet Oncol 2016), a standardized package of graphical and analytical assessments that depicts AEs longitudinally. In Alliance A151617, we applied ToxT analyses to a phase II randomized multicenter trial to characterize time course and severity of AEs associated with lenalidomide (L) alone or with rituximab (LR) in pts with relapsed follicular lymphoma (FL). Method(s): CALGB 50401 accrued 94 pts (L = 48, LR = 46). L was given in both study arms on days 1-21 of a 28-day cycle. ToxT plots depicting summary statistics or individual pt data over discrete time points were combined with longitudinal techniques (repeated measures modeling, time-to-event and areaunder-curve [AUC] analyses) including assessment of chronic low gr events. Result(s): Standard CTCAE analysis identified neutropenia and fatigue as the most common gr 3+ adverse events on L and LR (16% v 20%, respectively, for neutropenia, and 9% v 13% for fatigue). With ToxT analyses, bar charts of incidence and gr per cycle (c) define the AE trajectory, showing a steady rise in neutropenia incidence and gr in both arms as treatment continued. Among pts on LR (Panel A), 4/43[9.3%] experienced gr1 neutropenia at c1 and 11/ 31[35.4%] experienced gr