Long term follow-up (FU) of lenalidomide plus R-CHOP therapy in patients with newly diagnosed diffuse large b-cell lymphoma (DLBCL): Combined analysis from two phase 2 trials.

7562 Background: The combination of lenalidomide (Len) with Rituximab-CHOP (R2CHOP21) has been shown to be safe and effective. These early results [Nowakowski et al. JCO 2014, Vitolo et al. Lancet Oncol 2014] led to two randomized trials. However, durability of response and safety have not been reported. Here, we present the long-term FU in de novo DLBCL patients (pts) who received R2CHOP21 in two independent phase 2 studies. Methods: We included newly diagnosed DLBCL pts enrolled in two R2CHOP21 phase 2 trials, conducted by Mayo Clinic (MC) and Italian Lymphoma Foundation (FIL). All pts received R-CHOP21 plus Len at 25 mg/d for 10 days/cycle and 15 mg/d for 14 days/cycle in MC and FIL trial respectively. We analyzed the long term FU outcome in terms of progression-free survival (PFS), time to progression (TTP), overall survival (OS) and the cumulative incidence of late toxicities and second tumors. Results: 108 DLBCL pts (59 MC, 49 FIL) were included. Main characteristics were: median age 69 years (y) (25 (23%) ≥ 75 y), stage 3-4 in 94 (87.0%) and International Prognostic Index (IPI) ≥ 3 in 60 (55.6%). At a median FU of 5.1 y, 5y PFS was 65.4%, 5y TTP 69.9% and 5y OS 77.4%. In total, 31 pts have relapsed, with only 4 cases occurring beyond 3y and only 2 CNS relapses. 5y PFS in germinal center (GCB) lymphomas vs non-GCB was 55.8% vs 65.7%, 5y TTP 62.3 vs 68.0 and 5y OS 71.7% vs 75.3% respectively. Only 4 pts had grade (gr) 4-5 late toxicities (1 gr 5 sepsis and 3 gr 4 neutropenia). Milder toxicities were infections (N 5 (4.6%), only 1 gr 3), thrombosis (N 1, gr 2) and persistent neuropathy (N 3, gr 1-2). Second neoplasia were 8 (6.4%): 1 acute myeloid leukemia, 2 second lymphoma (T-cell) and 5 other solid tumors. Conclusions: Long term FU shows that R2CHOP21 efficacy was maintained with high rate of PFS, TTP and OS, considering high risk features of patients included. The addition of len to RCHOP appears to mitigate the negative prognostic impact of non-GCB phenotype. The incidence of second tumors was low and no new worrisome safety signals were seen. This long -term analysis will aid interpretation of early results from randomized clinical trials, expected to be reported in near future.