title: Lenalidomide therapy in myelofibrosis with myeloid metaplasia.
abstract: We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: William J
authors.initials: WJ
authors.lastname: Hogan
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Allred
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Catriona
authors.initials: C
authors.lastname: Byrne
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: McClure
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000750:Anemia, Myelophthisic / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D053614:Janus Kinase 2; D000077269:Lenalidomide; D008297:Male; D009389:Neovascularization, Pathologic / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D010976:Platelet Count; D017354:Point Mutation; D055728:Primary Myelofibrosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012074:Remission Induction; D017384:Sequence Deletion; D013163:Splenomegaly / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D011518:Proto-Oncogene Proteins; D013792:Thalidomide; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000077269:Lenalidomide