title: Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study.
abstract: OBJECTIVE
  Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL.
  
  
  METHODS
  Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+) DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP.
  
  
  RESULTS
  In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively).
  
  
  CONCLUSIONS
  R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL. nowakowski.grzegorz@mayo.edu.
authors.forename: Grzegorz S
authors.initials: GS
authors.lastname: Nowakowski
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Betsy
authors.initials: B
authors.lastname: LaPlant
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Reeder
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: James M
authors.initials: JM
authors.lastname: Foran
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Garth D
authors.initials: GD
authors.lastname: Nelson
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Thompson
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Candido E
authors.initials: CE
authors.lastname: Rivera
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Ivana N
authors.initials: IN
authors.lastname: Micallef
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Johnston
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Porrata
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.affiliation: Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D000069283:Rituximab; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; C571759:R-CHOP protocol; D000069283:Rituximab; D013792:Thalidomide; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077269:Lenalidomide; D011241:Prednisone