Comparative Outcomes of Relapsed Follicular Lymphoma Patients Treated with Novel Agents: A Multi-Center Analysis

Background: Follicular lymphoma (FL) is the most common indolent lymphoma and is generally characterized by prolonged survival with multiple relapses throughout the disease course. There is no standard of care as to the initial choice or sequencing of treatments for relapsed disease. Novel agents approved in the relapsed setting include lenalidomide in combination with rituximab (R2) and PI3K inhibitors (PI3Ki) including idelalisib, duvelisib, and copanlisib. However, there are no prospective data comparing the safety/efficacy of these novel agents to guide treatment selection. We aimed to examine the characteristics and outcomes of patients with relapsed follicular lymphoma treated with these novel agents. Methods: We conducted a retrospective analysis of adult patients with FL treated with commercially-available novel agents at 10 US academic cancer centers. Patients were excluded if they received one of these therapies as first line therapy or for the treatment of transformed disease. Treatment with lenalidomide or PI3Ki was determined by the treating physician, as was the decision to incorporate monoclonal antibody (mAb). For patients who received both classes of novel agent, baseline and treatment characteristics were grouped by first novel class used. The Fisher's Exact test was used to compare categorical variables and the Mann Whitney U test for continuous variables. Progression-free survival (PFS) was defined as time from the initiation of the first novel agent to progression of disease (POD), either FL or transformed disease, or death from any cause. Overall survival (OS) was defined as time from the initiation of the first novel agent to death from any cause. Outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: 98 patients were included. Available baseline characteristics at diagnosis are described in Table 1. The median time from the end of the last FL treatment to the start of the first novel agent was 12 months (range 0-79). The first novel agent was lenalidomide +/-mAb in 49% (n=48) of the patients and a PI3Ki +/- mAb in 51% (n=50) of patients. Idelalisib was the most commonly used PI3Ki (n=47) followed by copanlisib (n=2) and duvelisib (n=1). The median number of therapies prior to the first novel agent was 2 (range 1-8) and not significantly different between treatment classes. Reason for discontinuation of novel agent was significantly different between groups with greater discontinuations d