TY - JOUR
T1 - Interferon Therapy in Myelofibrosis
T2 - Systematic Review and Meta-analysis
AU - Bewersdorf, Jan Philipp
AU - Giri, Smith
AU - Wang, Rong
AU - Podoltsev, Nikolai
AU - Williams, Robert T.
AU - Rampal, Raajit K.
AU - Tallman, Martin S.
AU - Zeidan, Amer M.
AU - Stahl, Maximilian
N1 - Funding Information:
A.M.Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research and is supported by a National Cancer Institute (NCI) Cancer Clinical Investigator Team Leadership Award (CCITLA). Research reported in this publication was supported by the NCI of the National Institutes of Health under award P30 CA016359; and by a Cancer Center support grant/core grant to Memorial Sloan-Kettering Cancer Center (P30 CA008748). This work was supported by 2T32 CA009512-31 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
N.A.P. has consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squibb, and CTI BioPharma; and has received research funding (all to the institution) from Boehringer Ingelheim , Astellas Pharma , Daiichi-Sankyo , Sunesis Pharmaceuticals , Jazz Pharmaceuticals , Pfizer , Astex Pharmaceuticals , CTI BioPharma , Celgene , Genentech , AI Therapeutics , Samus Therapeutics , Arog Pharmaceuticals , and Kartos Therapeutics . M.S.T. has received research funding from AbbVie , Cellerant , Orsenix , ADC Therapeutics , and Biosight . R.K.R has received consulting fees from Constellation, Incyte, Celgene, Promedior, CTI BioPharma, Jazz Pharmaceuticals, Blueprint, and Stemline, and research funding from Incyte , Constellation , and Stemline . M.S.T. has received research funding from AbbVie , Cellerant , Orsenix , ADC Therapeutics , and Biosight ; honoraria for advisory board membership from AbbVie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, and Jazz Pharmaceuticals; and patents and royalties from UpToDate. A.M.Z. received research funding (all to the institution) from Celgene , Acceleron , AbbVie , Novartis , Otsuka , Pfizer , MedImmune /AstraZeneca, Boehringer Ingelheim , TrovaGene , Incyte , Takeda , and ADC Therapeutics ; has consulted for and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz Pharmaceuticals, Ariad, Incyte, Agios, Boehringer Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, TrovaGene, Ionis, Epizyme, and Takeda; and has received travel support for meetings from Pfizer, Novartis, and TrovaGene. The other authors have stated that they have no conflict of interest.
Funding Information:
N.A.P. has consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squibb, and CTI BioPharma; and has received research funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi-Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI BioPharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals, and Kartos Therapeutics. M.S.T. has received research funding from AbbVie, Cellerant, Orsenix, ADC Therapeutics, and Biosight. R.K.R has received consulting fees from Constellation, Incyte, Celgene, Promedior, CTI BioPharma, Jazz Pharmaceuticals, Blueprint, and Stemline, and research funding from Incyte, Constellation, and Stemline. M.S.T. has received research funding from AbbVie, Cellerant, Orsenix, ADC Therapeutics, and Biosight; honoraria for advisory board membership from AbbVie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, and Jazz Pharmaceuticals; and patents and royalties from UpToDate. A.M.Z. received research funding (all to the institution) from Celgene, Acceleron, AbbVie, Novartis, Otsuka, Pfizer, MedImmune/AstraZeneca, Boehringer Ingelheim, TrovaGene, Incyte, Takeda, and ADC Therapeutics; has consulted for and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz Pharmaceuticals, Ariad, Incyte, Agios, Boehringer Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, TrovaGene, Ionis, Epizyme, and Takeda; and has received travel support for meetings from Pfizer, Novartis, and TrovaGene. The other authors have stated that they have no conflict of interest.A.M.Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research and is supported by a National Cancer Institute (NCI) Cancer Clinical Investigator Team Leadership Award (CCITLA). Research reported in this publication was supported by the NCI of the National Institutes of Health under award P30 CA016359; and by a Cancer Center support grant/core grant to Memorial Sloan-Kettering Cancer Center (P30 CA008748). This work was supported by 2T32 CA009512-31. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10
Y1 - 2020/10
N2 - 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. Interferon (IFN)-α has been used for several decades for the treatment of myelofibrosis, with conflicting results. In this systematic review and meta-analysis of 10 studies with 141 patients, we found that IFN led to hematologic improvements in 49% of patients.
AB - 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. Interferon (IFN)-α has been used for several decades for the treatment of myelofibrosis, with conflicting results. In this systematic review and meta-analysis of 10 studies with 141 patients, we found that IFN led to hematologic improvements in 49% of patients.
KW - Adverse events
KW - Interferon
KW - Meta-analysis
KW - Myelofibrosis
KW - Systematic review
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U2 - 10.1016/j.clml.2020.05.018
DO - 10.1016/j.clml.2020.05.018
M3 - Article
C2 - 32669244
AN - SCOPUS:85087948957
SN - 2152-2669
VL - 20
SP - e712-e723
JO - Clinical Lymphoma
JF - Clinical Lymphoma
IS - 10
ER -
