AbstractBackgroundApproximately 40% patients of diffuse large B‐cell lymphoma (DLBCL) would develop disease recurrence/progression after first‐line R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single‐drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti‐tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long‐term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R‐CHOP treatment.MethodsThis retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6–8 cycles of R‐CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n= 141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide,n= 50) and drug‐free maintenance treatment (control,n= 91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression‐free survival (PFS) was taken as the primary outcome.ResultsOf the total 141 subjects, the median follow‐up time was 30.9 months (range, 5.7–68.9 months). The 2‐year PFS was 84% (95% CI: 74%–94%) in the lenalidomide group and 53% (95% CI: 43%–63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9 months (HR = 0.32; 95% CI: 0.16–0.63;p= 0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR = 0.42; 95% CI: 0.16–1.12;p= 0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1–2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3–4 adverse reaction.ConclusionTwo‐year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first‐line R‐CHOP treatment.