AbstractBackgroundThe treatment of high‐risk B‐cell lymphoma (BCL) remains a challenge, especially in the elderly.MethodsA total of 83 patients (median age 65 years), who have achieved a complete response after induction therapy, were divided into two groups: R2+ GM‐CSF regimen (lenalidomide, rituximab, granulocyte‐macrophage colony‐stimulating factor [GM‐CSF]) as maintenance therapy (n= 39) and observation (n= 44). The efficacy of the R2+ GM‐CSF regimen as maintenance in patient with high‐risk BCL was analyzed and compared with observation.ResultsThe number of natural killer cells in patients increased after R2+ GM‐CSF regimen administration (0.131 × 109/L vs. 0.061 × 109/L,p= 0.0244). Patients receiving the R2+ GM‐CSF regimen as maintenance therapy had longer remission (duration of response: 18.9 vs. 11.3 months,p= 0.001), and longer progression‐free survival (not reached (NR) vs. 31.7 months,p= 0.037), and overall survival (OS) (NR vs. NR,p= 0.015). The R2+ GM‐CSF regimen was safe and well tolerated. High international prognostic index score (p= 0.012), and high tumor burden (p= 0.005) appeared to be independent prognostic factors for worse PFS.ConclusionsThe maintenance therapy of R2+ GM‐CSF regimen may improve survival in high‐risk BCL patients, which might be modulated by amplification of natural killer cells. The efficacy of the R2+ GM‐CSF maintenance regimen has to be further validated in prospective random clinical trials.