Abstract
BACKGROUND/OBJECTIVES: Relapsed or refractory follicular lymphoma (rrFL) remains difficult to treat in elderly or frail patients who cannot tolerate standard-dose immuno-chemotherapy as well as novel therapies. Metronomic chemotherapy (mCHEMO) may offer sustained antitumor activity with reduced toxicity. This study assessed the clinical activity and safety of R-DEVEC or R-DEVEC-light in rrFL patients following lenalidomide discontinuation or ineligibility. METHODS: Data from the ReLLi Lymphoma Registry (2013-2025) were retrospectively analyzed. Eligible patients had rrFL after ≥1 prior therapy and initiated mCHEMO at least six months before data cutoff. Thirteen patients received DEVEC or the etoposide-free DEVEC-light regimen; all but one also received rituximab. Responders received maintenance vinorelbine, low-dose prednisone, and rituximab, followed by vinorelbine-only maintenance until progression or intolerance. Responses were assessed by CT after cycle two and PET/CT at completion of six induction cycles. RESULTS: median age was 77 years (range 58-92); most patients were frail and had advanced disease. At the end of induction, 84% achieved remission (46% CR, 38% PR), with three PR converting to CR during maintenance. After a median follow-up of 27 months, the PFS was 42% (95CI 15-69%) and the OS 73% (95CI 47-100%). A transformation occurred in one patient; the main toxicity was grade 3 neutropenia (31%). DEVEC-light showed improved tolerability versus full DEVEC, with manageable infections and rare discontinuations. CONCLUSIONS: Metronomic R-DEVEC-light is a feasible and effective disease-controlling strategy for frail, heavily pretreated rrFL patients who do not tolerate lenalidomide and are excluded from modern therapies. This schedule warrants further prospective evaluation and exploration in combination with targeted agents.