Real-world Data For Lenalidomide Maintenance In Responding Patients With Diffuse Large B-cell Lymphoma

Background Approximately 40% patients of diffuse large B-cell lymphoma（DLBCL）would develop relapse/refractory disease after first-line immunochemotherapy and those patients with highly poor prognosis.Maintenance therapy with a single drug may be an effective strategy for prolonging survival in patients with complete response（CR）or partial response（PR）after first-line induction 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.Considering its controllable toxicity,Lenalidomide is a promising drug in long-term maintenance therapy.This study aims at evaluating the clinical efficacy of Lenalidomide in the maintenance therapy of DLBCL.Methods This retrospective study was devised in DLBCL cases who obtained CR or PR following 6-8 cycles of R-CHOP treatment between January 1,2015 and July 31,2019.Patients（n = 141）included were assigned to receive Lenalidomide maintenance treatment（Lenalidomide,n = 50）and drug-free maintenance treatment（Control,n = 91）respectively.Lenalidomide was provided orally at 25 mg/d（dose adjustment based on adverse reactions）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.Results A total of 141 patients were included,and the median follow-up time was 30.9months（range,5.7-68.9 months）.The 2-year PFS was 84%（95% CI: 74-94%）in the Lenalidomide group compared to 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）.There was no remarkable difference in overall survival（OS）between the two groups（HR,0.42;95% CI: 0.16-1.12;P = 0.08）.Comparing the post-relapse OS of the 56 patients who developed relapse,the median post-relapse OS was 18.9 months（95% CI: 2.9-34.8 months）and 21.7 months（95% CI: 10.0-33.5 months）in the Lenalidomide and Control group,respectively（P =0.21）.Central nervous system（CNS）recurrence happened in 5 patients（5.5%）of the Control group,while there were no patients in the Lenalidomide group.Additionally,neutropenia and cutaneous reactions were the most common Grade I/II adverse reactions after Lenalidomide treatment,and neutropenia was the most frequent Grade III/IV adverse reaction.Conclusion This study suggests that Lenalidomide maintenance therapy can significantly prolong the PFS of DLBCL patients who obtained CR/PR after first-line R-CHOP treatment,and the toxicity of Lenalidomide is tolerable.The PFS benefit of Lenalidomide has not yet translated into an OS benefit,which may be attributed to successful salvage therapy after relapse in the Control group.Lenalidomide has the potential to prevent CNS recurrence,however,the appropriate timing of application and the best applicable population remain to be explored.