Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Is It a Valid Treatment Option?

Oncologist. 2016 Sep;21(9):1107-12. doi: 10.1634/theoncologist.2016-0103. Epub 2016 Jul 5.


Background: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease. Prospective clinical trials have demonstrated that lenalidomide is an effective and safe treatment option, especially for non-germinal center B-cell (non-GCB) DLBCL. However, routine clinical data are lacking, which is why we provide the results of the so-far largest relapsed/refractory (R/R) DLBCL real-life analysis.

Methods: We retrospectively assessed 123 R/R DLBCL patients who received either 15 or 25 mg/day of lenalidomide from January 2006 to January 2015.

Results: During a median follow-up period of 4.5 years, complete remission was achieved in 32% and a partial remission in 33% non-GCB patients compared with 0% and 3% in the GCB group (p < .001 and .001, respectively), with median response durations of 15 and 5 months, respectively (p < .001). Lenalidomide at 25 mg was superior to 15 mg in terms of response (complete remission 21% and partial remission 23% vs. 0% and 8%; p = .007 and .05) and median response duration (10 vs. 4 months; p = .03). Toxicity was limited and reversible. Median progression-free survival differed between non-GCB and GCB patients (37 vs. 30 months; p < .001) and between the two dosages (24 vs. 34 months; p = .002). However, overall survival was similar between the subgroups (38-42 months).

Conclusion: We provide evidence that lenalidomide is a valid treatment option for R/R DLBCL, with limited and reversible toxicity, and is more efficient in non-GCB DLBCL and at higher doses.

Implications for practice: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease; hence, novel therapeutic approaches are urgently needed. This study confirms that lenalidomide is a valid and well-tolerated treatment option for relapsed/refractory (R/R) DLBCL. Superior outcomes were observed in non-germinal center B-cell (GCB) DLBCL, probably because of inhibition of the nuclear factor-κB pathway. Similarly, high drug doses resulted in greater clinical benefits. Overall, lenalidomide is a suitable therapeutic option for R/R DLBCL, especially in non-GCB DLBCL, and 25 mg/day dosing should be preferred.

Keywords: Diffuse large B-cell lymphoma; Immunomodulatory drug; Lenalidomide; Relapsed/refractory lymphoma.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Lenalidomide
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Remission Induction
  • Secondary Prevention / methods
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Treatment Outcome


  • Thalidomide
  • Lenalidomide