Jan Philipp Bewersdorf1, Smith Giri2, Rong Wang3, Nikolai Podoltsev4, Robert T Williams5, Raajit K Rampal6, Martin S Tallman6, Amer M Zeidan4, Maximilian Stahl7. 1. Department of Internal Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT. 2. Division of Hematology and Oncology, University of Alabama School of Medicine, Birmingham, AL. 3. Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT; Department of Chronic Disease Epidemiology, School of Public Health, Yale University, New Haven, CT. 4. Department of Internal Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT; Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT. 5. Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY. 6. Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY. 7. Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: stahlm@mskcc.org.
Abstract
BACKGROUND: Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to acute myeloid leukemia, and constitutional symptoms. For over 3 decades, various formulations of interferon (IFN) have been used for the treatment of MF, with variable results, and the role of IFN in the treatment of MF is evolving. PATIENTS AND METHODS: For this systematic review and meta-analysis, Medline and Embase via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception through March 2019 for studies of pegylated IFN (peg-IFN) and non-peg-IFN in MF patients. The primary outcome of overall response rate was defined as a composite of complete response, partial response, complete hematologic response, and partial hematologic response. Random-effects models were used to pool overall response rate, and metaregression analyses were performed to compare peg-IFN and non--peg-IFN formulations. RESULTS: Among the 10 studies with 141 MF patients included, the overall response rate was 49.9% (95% confidence interval [CI], 30.4-69.3), and there was no statistically significant difference (P = .99) between peg-IFN (50.0%; 95% CI, 26.2-73.9; I2 = 76.9%) and non-peg-IFN (49.6%; 95% CI, 20.5-79.0; I2 = 56.7%). Treatment discontinuation resulting from adverse events was common with non-peg-IFN at 35.8% (95% CI, 3.5-68.1) per year, and less in the one study on peg-IFN (0.5% per year). CONCLUSION: IFN can lead to hematologic improvements in a subset of MF patients, but study quality is limited and heterogenous. Biomarkers predicting response to IFN and formulations with improved tolerability are needed.
BACKGROUND:Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to acute myeloid leukemia, and constitutional symptoms. For over 3 decades, various formulations of interferon (IFN) have been used for the treatment of MF, with variable results, and the role of IFN in the treatment of MF is evolving. PATIENTS AND METHODS: For this systematic review and meta-analysis, Medline and Embase via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception through March 2019 for studies of pegylated IFN (peg-IFN) and non-peg-IFN in MF patients. The primary outcome of overall response rate was defined as a composite of complete response, partial response, complete hematologic response, and partial hematologic response. Random-effects models were used to pool overall response rate, and metaregression analyses were performed to compare peg-IFN and non--peg-IFN formulations. RESULTS: Among the 10 studies with 141 MF patients included, the overall response rate was 49.9% (95% confidence interval [CI], 30.4-69.3), and there was no statistically significant difference (P = .99) between peg-IFN (50.0%; 95% CI, 26.2-73.9; I2 = 76.9%) and non-peg-IFN (49.6%; 95% CI, 20.5-79.0; I2 = 56.7%). Treatment discontinuation resulting from adverse events was common with non-peg-IFN at 35.8% (95% CI, 3.5-68.1) per year, and less in the one study on peg-IFN (0.5% per year). CONCLUSION:IFN can lead to hematologic improvements in a subset of MF patients, but study quality is limited and heterogenous. Biomarkers predicting response to IFN and formulations with improved tolerability are needed.
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