title: Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium.
abstract: OBJECTIVE
  Lenalidomide is an immunomodulatory agent with therapeutic activity in chronic lymphocytic leukemia (CLL). In preclinical models, lenalidomide acted synergistically with rituximab. The CLL Research Consortium initiated a phase II study to evaluate this combination in treatment-naive patients.
  
  
  METHODS
  Lenalidomide was initiated at 2.5 mg/day and was escalated based on treatment tolerability to a maximum of 10 mg/day, for 21 days/cycle, for a maximum of seven cycles. Rituximab was administered at the end of cycle 1 and was continued for seven cycles. Patients received allopurinol and aspirin for prophylaxis.
  
  
  RESULTS
  Sixty-nine patients enrolled onto one of two age-specific strata; patients' median age was 56 and 70 years for arms A and B, respectively. Patients in the older-patient stratum more frequently had elevated serum beta-2 microglobulin levels, high-risk Rai stage, and were less likely to complete the maximum planned therapy. Adverse events were similar in the two arms. Nonhematologic toxicity was predominantly at grade 1/2, and neutropenia was the most common hematologic adverse event. The response rate for arm A was 95%, with 20% complete responses (CRs) and 20% nodular partial responses. Of arm B patients, 78% achieved a response, of which 11% were CRs. Median progression-free survival (PFS) was 19 months for the younger cohort and 20 months for the older cohort.
  
  
  CONCLUSIONS
  Intrapatient dose-escalation was safe. The majority of patients reached the maximum lenalidomide dose and experienced a response to a defined seven-cycle course of lenalidomide and rituximab therapy. Despite differences in baseline characteristics and the response rate between the two strata, the PFS did not differ.
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Danelle F
authors.initials: DF
authors.lastname: James
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Barrientos
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Januario E
authors.initials: JE
authors.lastname: Castro
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Andrew
authors.initials: A
authors.lastname: Greaves
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Johnson
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Laura Z
authors.initials: LZ
authors.lastname: Rassenti
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Kanti R
authors.initials: KR
authors.lastname: Rai
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.affiliation: Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH. tkipps@ucsd.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011961:Receptors, Fc / Q000235:genetics; D012307:Risk Factors; D000069283:Rituximab; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D011961:Receptors, Fc; D000069283:Rituximab; D013792:Thalidomide; D000077269:Lenalidomide