Document Detail


Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis.
MedLine Citation:
PMID:  19720904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate the safety and efficacy of the combination of lenalidomide and prednisone in patients with myelofibrosis (MF).
PATIENTS AND 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%).
CONCLUSION: The combination of lenalidomide and prednisone induces durable clinical, molecular, and pathologic responses in MF.
Authors:
Alfonso Quintás-Cardama; Hagop M Kantarjian; Taghi Manshouri; Deborah Thomas; Jorge Cortes; Farhad Ravandi; Guillermo Garcia-Manero; Alessandra Ferrajoli; Carlos Bueso-Ramos; Srdan Verstovsek
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article     Date:  2009-08-31
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  27     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-30     Completed Date:  2009-10-26     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4760-6     Citation Subset:  IM    
Affiliation:
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00352794
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Anemia / chemically induced
Antineoplastic Agents / administration & dosage,  therapeutic use
Drug Therapy, Combination
Enzyme-Linked Immunosorbent Assay
Female
Fibroblast Growth Factor 2 / blood
Glucocorticoids / therapeutic use
Humans
Janus Kinase 2 / genetics
Male
Middle Aged
Mutation
Neutropenia / chemically induced
Platelet-Derived Growth Factor / metabolism
Prednisone / therapeutic use*
Primary Myelofibrosis / blood,  drug therapy*,  genetics
Thalidomide / adverse effects,  analogs & derivatives*,  therapeutic use
Thrombocytopenia / chemically induced
Transforming Growth Factor beta / blood
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Glucocorticoids; 0/Platelet-Derived Growth Factor; 0/Transforming Growth Factor beta; 103107-01-3/Fibroblast Growth Factor 2; 191732-72-6/lenalidomide; 50-35-1/Thalidomide; 53-03-2/Prednisone; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.2/JAK2 protein, human

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