Lenalidomide therapy in myelofibrosis with myeloid metaplasia.
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.
Tefferi
Ayalew
A
Division of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. tefferi.ayalew@mayo.edu
Cortes
Jorge
J
Verstovsek
Srdan
S
Mesa
Ruben A
RA
Thomas
Deborah
D
Lasho
Terra L
TL
Hogan
William J
WJ
Litzow
Mark R
MR
Allred
Jacob B
JB
Jones
Dan
D
Byrne
Catriona
C
Zeldis
Jerome B
JB
Ketterling
Rhett P
RP
McClure
Rebecca F
RF
Giles
Francis
F
Kantarjian
Hagop M
HM
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
D006454:Hemoglobins; D011518:Proto-Oncogene Proteins; D013792:Thalidomide; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000077269:Lenalidomide