Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: the FIL_ReRi Phase 2 Study.

Treatment of diffuse large B-cell lymphoma (DLBCL) in elderly patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. The Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a two-stage single arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2)in ≥ 70-year-old untreated frail DLBCL patients. Frailty was prospectively defined according to a simplified geriatric assessment tool. Patients were given a maximum of 6 28-day cycles of 20 mg oral lenalidomide on days 2-22 and intravenous rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients in partial (PR) or complete response (CR) at cycle 6 were given lenalidomide 10 mg/d on days 1-21 in q28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) after cycle 6; the co-primary endpoint was the rate of grade 3-4 extra-hematological toxicity. The ORR was 50.8%, with 27.7% of CR. After a median follow-up of 24 months, median progression-free survival (PFS) was 14 months, and two-year duration of response was 64%. Thirty-four patients experienced extra-hematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3. Activity of R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach of elderly frail patients with DLBCL. The trial was registered at ClinicalTrials.gov as NCT01805557.