title: Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis.
abstract: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a MPN characterized by bone marrow fibrosis, cytopenias, splenomegaly and constitutional symptoms. Pomalidomide, an immune-modifying drug, is reported to improve anaemia and thrombocytopenia in some patients with MPN-associated myelofibrosis. We designed a phase 2 study of pomalidomide in patients with MPN-associated myelofibrosis and anaemia and/or thrombocytopenia and/or neutropenia. Subjects received pomalidomide 2.0 mg/day in cohort 1 (n=38) or 0.5 mg/day in cohort 2 (n=58). Prednisolone was added if there was no response after 3 months in cohort 1 and based on up-front randomization in cohort 2 if there was no response at 3 or 6 months. Response rates were 39% (95% confidence interval (CI), 26-55%) in cohort 1 and 24% (95% CI, 15-37%) in cohort 2. In a multivariable logistic regression model pomalidomide at 2.0 mg/day (odds ratio (OR), 2.62; 95% CI, 1.00-6.87; P=0.05) and mutated TET2 (OR, 5.07; 95% CI, 1.16-22.17; P=0.03) were significantly associated with responses. Median duration of responses was 13.0 months (range 0.9-52.7). There was no significant difference in response rates or duration in subjects receiving or not receiving prednisolone. Clinical trial MPNSG 01-09 is registered at ClinicalTrials.gov (NCT00949364) and clinicaltrialsregister.eu (EudraCT Number: 2009-010738-23).
authors: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.|NCT Trial Center, National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors: R F
authors: RF
authors: Schlenk
authors: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
authors: F
authors: F
authors: Stegelmann
authors: Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
authors: A
authors: A
authors: Reiter
authors: Department of Internal Medicine IV, University Hospital Aachen, Aachen, Germany.
authors: E
authors: E
authors: Jost
authors: Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany.
authors: N
authors: N
authors: Gattermann
authors: Department of Hematology and Oncology, Stauferklinikum Mutlangen, Mutlangen, Germany.
authors: H
authors: H
authors: Hebart
authors: Department of Internal Medicine I, University Hospital and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors: C
authors: C
authors: Waller
authors: Internal Medicine II, Jena University Hospital, Jena, Germany.
authors: A
authors: A
authors: Hochhaus
authors: Department of Internal Medicine I, University Hospital Dresden and GP Hematology and Oncology, Dresden, Germany.
authors: U
authors: U
authors: Platzbecker
authors: Department of Internal Medicine II, University Hospital Hamburg, Hamburg, Germany.
authors: P
authors: P
authors: Schafhausen
authors: Department of Hematology and Oncology, Charité, Campus Benjamin Franklin, Berlin, Germany.
authors: I W
authors: IW
authors: Blau
authors: Center of Outpatient Hematology and Oncology, Bonn, Germany.
authors: W
authors: W
authors: Verbeek
authors: Department of Hematology and Oncology, University Hospital Magdeburg, Magdeburg, Germany.
authors: F H
authors: FH
authors: Heidel
authors: Department of Pathology, University of Freiburg, Freiburg, Germany.
authors: M
authors: M
authors: Werner
authors: Department of Pathology, Hannover Medical School, Hannover, Germany.
authors: H
authors: H
authors: Kreipe
authors: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
authors: V
authors: V
authors: Teleanu
authors: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
authors: A
authors: A
authors: Benner
authors: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
authors: H
authors: H
authors: Döhner
authors: Department of Oncology, Klinikum Minden, Minden, Germany.
authors: M
authors: M
authors: Grießhammer
authors: Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
authors: K
authors: K
authors: Döhner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015415:Biomarkers; D002871:Chromosome Banding; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D013792:Thalidomide; D011239:Prednisolone; C467566:pomalidomide