title: Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial.
abstract: BACKGROUND
  Standard treatments for indolent non-Hodgkin lymphomas are often toxic, and most patients ultimately relapse. Lenalidomide, an immunomodulatory agent, is effective as monotherapy for relapsed indolent non-Hodgkin lymphoma. We assessed the efficacy and safety of lenalidomide plus rituximab in patients with untreated, advanced stage indolent non-Hodgkin lymphoma.
  
  
  METHODS
  In this phase 2 trial, undertaken at one instution, patients with follicular lymphoma and marginal zone lymphoma were given lenalidomide, orally, at 20 mg/day on days 1-21 of each 28-day cycle. For patients with small lymphocytic lymphoma, dosing began at 10 mg/day to avoid tumour flare, with an escalation of 5 mg/month to 20 mg/day. Rituximab was given at 375 mg/m(2) as an intravenous infusion on day 1 of each cycle. Patients responding after six cycles could continue therapy for up to 12 cycles. The primary endpoint was overall response, defined as the proportion of patients who achieved a partial or complete response; patients were assessed for response if they had any post-baseline tumour assessment. This trial is registered with ClinicalTrials.gov, number NCT00695786.
  
  
  RESULTS
  110 patients with follicular lymphoma (n=50), marginal zone lymphoma (n=30), and small lymphocytic lymphoma (n=30) were enrolled from June 30, 2008, until Aug 12, 2011. 93 of 103 evaluable patients had an overall response (90%, 95% CI 83-95). Complete responses occurred in 65 (63%, 95% CI 53-72) and partial responses in 28 patients (27%, 19-37). Of 46 evaluable patients with follicular lymphoma, 40 (87%) patients had a complete response and five (11%) had a partial response. Of 27 evaluable patients with marginal zone lymphoma, 18 (67%) had a complete response and six (22%) had a partial response. Of 30 evaluable patients with small lymphocytic lymphoma, seven (23%) had a complete response and 17 (57%) had a partial response. The most common grade 3 or 4 adverse events were neutropenia (38 [35%] of 110 patients), muscle pain (ten [9%]), rash (eight [7%]), cough, dyspnoea, or other pulmonary symptoms (five [5%]), fatigue (five [5%]), thrombosis (five [5%]), and thrombocytopenia (four [4%]).
  
  
  CONCLUSIONS
  Lenalidomide plus rituximab is well tolerated and highly active as initial treatment for indolent non-Hodgkin lymphoma. An international phase 3 study (NCT01476787) to compare this regimen with chemotherapy in patients with untreated follicular lymphoma is in progress.
  
  
  BACKGROUND
  Celgene Corporation and Richard Spencer Lewis Memorial Foundation and Cancer Center Support Grant.
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: nfowler@mdanderson.org.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Fowler
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R Eric
authors.initials: RE
authors.lastname: Davis
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Rawal
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Loretta
authors.initials: L
authors.lastname: Nastoupil
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Fanale
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Westin
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jatin
authors.initials: J
authors.lastname: Shah
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Turturro
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Claret
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Veerabhadran
authors.initials: V
authors.lastname: Baladandayuthapani
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tariq
authors.initials: T
authors.lastname: Muzzafar
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kenneth Y
authors.initials: KY
authors.lastname: Tsai
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D000069283:Rituximab; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D013792:Thalidomide; D000077269:Lenalidomide