title: Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis.
abstract: OBJECTIVE
  To investigate the safety and efficacy of the combination of lenalidomide and prednisone in patients with myelofibrosis (MF).
  
  
  METHODS
  Forty patients with MF were treated. Therapy consisted of lenalidomide 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) on days 1 through 21 of a 28-day cycle for six cycles, in combination with prednisone 30 mg/d orally during cycle 1, 15 mg/d during cycle 2, and 15 mg/d every other day during cycle 3. Lenalidomide therapy was continued indefinitely in patients exhibiting clinical benefit.
  
  
  RESULTS
  The median follow-up was 22 months (range, 6 to 27). Responses were recorded in 12 patients (30%) and are ongoing in 10 (25%). The median time to response was 12 weeks (range, 2 to 32). According to the International Working Group for Myelofibrosis Research and Treatment consensus criteria, three patients (7.5%) had partial response and nine patients (22.5%) had clinical improvement durable for a median of 18 months (range, 3.5 to 24+). Overall response rates were 30% for anemia and 42% for splenomegaly. Moreover, 10 of 11 assessable responders who started therapy with reticulin fibrosis grade 4 experienced reductions to at least a score of 2. All eight JAK2(V617F)-positive responders experienced a reduction of the baseline mutant allele burden, which was greater than 50% in four, including one of whom the mutation became undetectable. Grade 3 to 4 hematologic adverse events included neutropenia (58%), anemia (42%), and thrombocytopenia (13%).
  
  
  CONCLUSIONS
  The combination of lenalidomide and prednisone induces durable clinical, molecular, and pathologic responses in MF.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009503:Neutropenia / Q000139:chemically induced; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011241:Prednisone / Q000627:therapeutic use*; D055728:Primary Myelofibrosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000077269:Lenalidomide; D011241:Prednisone