title: Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype.
abstract: BACKGROUND
  There is a need to develop novel therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and to identify biomarkers predictive for therapeutic response. Lenalidomide was previously shown to induce an overall response rate (ORR) of 28% in patients with relapsed/refractory DLBCL. It is currently unknown if response rates differ between patients with different DLBCL subtypes.
  
  
  METHODS
  The authors retrospectively evaluated clinical outcomes of patients with germinal center B-cell-like versus nongerminal center B-cell-like DLBCL treated with salvage lenalidomide at 4 academic institutions.
  
  
  RESULTS
  Forty patients with relapsed/refractory DLBCL were included (24 men; 16 women; median age, 66 years; median of 4 prior treatments, including rituximab chemotherapy). Patients were classified as germinal center B-cell-like (n = 23) or nongerminal center B-cell-like (n = 17) DLBCL according to the Hans algorithm. The subgroups were similar in terms of stage, international prognostic index score, prior number of treatments, and rituximab resistance. A significant difference in clinical response to lenalidomide was observed in nongerminal center B-cell-like versus germinal center B-cell-like patients. ORR was 52.9% versus 8.7% (P = .006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P = .004), although no difference in OS was observed between nongerminal center B-cell-like and germinal center B-cell-like DLBCL patients.
  
  
  CONCLUSIONS
  The data suggest that the 2 major subgroups of patients with DLBCL (germinal center B cell and nongerminal center B cell) have different antitumor responsiveness to lenalidomide in the relapsed/refractory setting. A large international trial (NCT01197560) has been opened to enrollment in an attempt to prospectively validate these retrospective observations.
authors.affiliation: Department of Medical Oncology and Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA. Francisco.hernandez@roswellpark.org
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Hernandez-Ilizaliturri
authors.forename: George
authors.initials: G
authors.lastname: Deeb
authors.forename: Pier L
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Farhana
authors.initials: F
authors.lastname: Malik
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Myron S
authors.initials: MS
authors.lastname: Czuczman
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D000077269:Lenalidomide; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide