Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis

• Published in: Leukemia Vol. 31; no. 4; pp. 889 - 895
• Main Authors: Schlenk, R F, Stegelmann, F, Reiter, A, Jost, E, Gattermann, N, Hebart, H, Waller, C, Hochhaus, A, Platzbecker, U, Schafhausen, P, Blau, I W, Verbeek, W, Heidel, F H, Werner, M, Kreipe, H, Teleanu, V, Benner, A, Döhner, H, Grießhammer, M, Döhner, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2017; Nature Publishing Group
• Subjects: 692/308/2779/109/1941; 692/308/2779/109/1943; 692/699/67/1990/2331; 692/700/565/1436; Aged; Aged, 80 and over; Alleles; Anemia; Biomarkers; Blood; Bone marrow; Cancer Research; Chromosome Banding; Complications and side effects; Confidence intervals; Critical Care Medicine; Dosage and administration; Dose-response relationship (Biochemistry); Drug dosages; Drug therapy; Female; Fibrosis; Genetic aspects; Hematology; Hemoglobin; Hospitals; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Intensive; Internal Medicine; Leukemia; Logistic regression; Male; Medical research; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myelofibrosis; Myeloproliferative disorders; Myeloproliferative Disorders - complications; Myeloproliferative Disorders - diagnosis; Myeloproliferative Disorders - genetics; Neutropenia; Oncology; original-article; Patients; Phenotype; Prednisolone; Prednisolone - administration & dosage; Prednisolone - adverse effects; Prednisolone - therapeutic use; Primary Myelofibrosis - diagnosis; Primary Myelofibrosis - drug therapy; Primary Myelofibrosis - etiology; Regression models; Response rates; Risk factors; Splenomegaly; Statistical analysis; Thalidomide - administration & dosage; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Thalidomide - therapeutic use; Thrombocytopenia; Toxicity; Treatment Outcome; Tumors; Germany; Aachen Germany
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2016.299

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)