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: Ayalew Tefferi, Jorge Cortes, Srdan Verstovsek, Ruben A Mesa, Deborah Thomas, Terra L Lasho, William J Hogan, Mark R Litzow, Jacob B Allred, Dan Jones, Catriona Byrne, Jerome B Zeldis, Rhett P Ketterling, Rebecca F McClure, Francis Giles, Hagop M Kantarjian
• Journal: Blood (Blood) Vol. 108 Issue 4 Pg. 1158-64 (Aug 15 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16609064 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Hemoglobins
• Proto-Oncogene Proteins
• Thalidomide
• Protein-Tyrosine Kinases
• JAK2 protein, human
• Janus Kinase 2
• Lenalidomide

Topics

• Administration, Oral
• Adult
• Aged
• Anemia (blood, complications, drug therapy, genetics, pathology)
• Anemia, Myelophthisic (blood, complications, drug therapy, genetics, pathology)
• Female
• Hemoglobins (analysis)
• Humans
• Janus Kinase 2
• Lenalidomide
• Male
• Neovascularization, Pathologic (blood, complications, drug therapy, genetics, pathology)
• Neutropenia (blood, chemically induced, genetics, pathology)
• Platelet Count
• Point Mutation
• Primary Myelofibrosis (blood, complications, drug therapy, genetics, pathology)
• Protein-Tyrosine Kinases (genetics)
• Proto-Oncogene Proteins (genetics)
• Remission Induction
• Sequence Deletion
• Splenomegaly (blood, complications, drug therapy, genetics, pathology)
• Thalidomide (administration & dosage, adverse effects, analogs & derivatives)
• Thrombocytopenia (blood, chemically induced, drug therapy, genetics, pathology)
• Time Factors