title: Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Is It a Valid Treatment Option?
abstract: 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.
  
  
  
  We retrospectively assessed 123 R/R DLBCL patients who received either 15 or 25 mg/day of lenalidomide from January 2006 to January 2015.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Human Pathology, University of Messina, Messina, Italy Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina, Italy Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA patriziamondello@hotmail.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mondello
authors.affiliation: Internal Medicine V, Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Normann
authors.initials: N
authors.lastname: Steiner
authors.affiliation: Internal Medicine V, Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Willenbacher
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ferrero
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ghione
authors.affiliation: Department of Hematology and Center for Bone Marrow Transplantation, Ospedale di Bolzano, Bolzano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marabese
authors.affiliation: Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pitini
authors.affiliation: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Internal Medicine V, Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria Department of Hematology and Center for Bone Marrow Transplantation, Ospedale di Bolzano, Bolzano, Italy.
authors.forename: Michael
authors.initials: M
authors.lastname: Mian
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D055502:Secondary Prevention / Q000379:methods; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide
keywords: Diffuse large B-cell lymphoma; Immunomodulatory drug; Lenalidomide; Relapsed/refractory lymphoma