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Chronic myeloproliferative neoplasms

Interferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis

Leukemia volume 35, pages 1643–1660 (2021)Cite this article

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Abstract

Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6–84.1%, CHR: 59.0% [51.5%–66.1%]) and 76.7% (67.4–84.0%; CHR: 48.5% [37.8–59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.

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Fig. 1: Flow chart showing study selection as per the MOOSE guidelines.
Fig. 2: Response to non-pegylated IFN (IFN) and pegylated IFN (peg-IFN) in ET.
Fig. 3: Response to non-pegylated IFN (IFN) and pegylated IFN (peg-IFN) in PV.
Fig. 4: Rate of thromboembolic events (per patient year).
Fig. 5: Discontinuation rate of non-pegylated IFN (IFN) and pegylated IFN (peg-IFN) therapy (for all patients while on study).

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Acknowledgements

AMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also 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 Number P30 CA016359 and Cancer Center Support Grant/Core Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748) The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. These authors jointly supervised this work: Amer M. Zeidan, Maximilian Stahl and both served as senior co-authors

Authors and Affiliations

  1. Department of Internal Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT, USA

    Jan Philipp Bewersdorf, Nikolai Podoltsev & Amer M. Zeidan

  2. Division of Hematology and Oncology, University of Alabama School of Medicine, Birmingham, AL, USA

    Smith Giri

  3. Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT, USA

    Rong Wang, Nikolai Podoltsev & Amer M. Zeidan

  4. Department of Chronic Disease Epidemiology, School of Public Health, Yale University, New Haven, CT, USA

    Rong Wang

  5. Rockefeller University, New York, NY, USA

    Robert T. Williams

  6. Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Martin S. Tallman, Raajit K. Rampal & Maximilian Stahl

Authors
  1. Jan Philipp Bewersdorf
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  2. Smith Giri
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  3. Rong Wang
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  4. Nikolai Podoltsev
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  5. Robert T. Williams
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  6. Martin S. Tallman
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  7. Raajit K. Rampal
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  8. Amer M. Zeidan
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  9. Maximilian Stahl
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Corresponding author

Correspondence to Maximilian Stahl.

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Conflict of interest

NAP consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squib and CTI biopharma. NAP 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. MST has received research funding from Abbvie, Cellerant, Orsenix, ADC Therapeutics, and Biosight. RKR has received consulting fees from: Constellation, Incyte, Celgene, Promedior, CTI, Jazz Pharmaceuticals, Blueprint, Stemline, and research funding from Incyte, Constellation, Stemline. MST has received honoraria for MST has received research funding from Abbvie, Cellerant, Orsenix, ADC Therapeutics, and Biosight. MST has received honoraria for advisory board membership from Abbvie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, and Jazz Pharma. MST received patents and royalties from UpToDate. AMZ received research funding (institutional) from Celgene, Acceleron, Abbvie, Novartis, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics. AMZ had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz, Ariad, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, Trovagene, Ionis, Epizyme, Amgen, Tyme, Janssen, and Takeda. AMZ received travel support for meetings from Pfizer, Novartis, and Trovagene. None of these relationships were related to the development of this manuscript. All other authors report no relevant disclosures/competing interests.

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Bewersdorf, J.P., Giri, S., Wang, R. et al. Interferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis. Leukemia 35, 1643–1660 (2021). https://doi.org/10.1038/s41375-020-01020-4

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