Blood Res 2021; 56(S1):
Published online April 30, 2021
https://doi.org/10.5045/br.2021.2020334
© The Korean Society of Hematology
Correspondence to : Jong-Ho Won, M.D., Ph.D. Division of Hematology & Medical Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea
E-mail: jhwon@schmc.ac.kr
*This study was supported by a grant from the Soonchunhyang University Research Fund.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell malignancies. Chronic inflammation and a dysregulated immune system are central to the pathogenesis and progression of MPNs. Interferon alpha (IFNα) was first used for the treatment of MPNs approximately 40 years ago. It has significant antiviral effects and plays a role in anti-proliferative, pro-apoptotic, and immunomodulatory responses. IFNα is an effective drug that can simultaneously induce significant rates of clinical, hematological, molecular, and histopathological responses, suggesting that the disease may be cured in some patients. However, its frequent dosage and toxicity profile are major barriers to its widespread use. Pegylated IFNα (peg-IFNα), and more recently, ropeginterferon alpha-2b (ropeg-IFNα-2b), are expected to overcome these drawbacks. The objective of this article is to discuss the clinical role of IFNα in Philadelphia-negative MPNs through a review of recent studies. In particular, it is expected that new IFNs, such as peg-IFNα and ropeg-IFNα-2b, with lower rates of discontinuation due to fewer adverse effects, will play important clinical roles.
Keywords Myeloproliferative disorder, Interferon alpha, Therapy
Blood Res 2021; 56(S1): S44-S50
Published online April 30, 2021 https://doi.org/10.5045/br.2021.2020334
Copyright © The Korean Society of Hematology.
Seug Yun Yoon, Jong-Ho Won
Division of Hematology & Medical Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
Correspondence to:Jong-Ho Won, M.D., Ph.D. Division of Hematology & Medical Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea
E-mail: jhwon@schmc.ac.kr
*This study was supported by a grant from the Soonchunhyang University Research Fund.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell malignancies. Chronic inflammation and a dysregulated immune system are central to the pathogenesis and progression of MPNs. Interferon alpha (IFNα) was first used for the treatment of MPNs approximately 40 years ago. It has significant antiviral effects and plays a role in anti-proliferative, pro-apoptotic, and immunomodulatory responses. IFNα is an effective drug that can simultaneously induce significant rates of clinical, hematological, molecular, and histopathological responses, suggesting that the disease may be cured in some patients. However, its frequent dosage and toxicity profile are major barriers to its widespread use. Pegylated IFNα (peg-IFNα), and more recently, ropeginterferon alpha-2b (ropeg-IFNα-2b), are expected to overcome these drawbacks. The objective of this article is to discuss the clinical role of IFNα in Philadelphia-negative MPNs through a review of recent studies. In particular, it is expected that new IFNs, such as peg-IFNα and ropeg-IFNα-2b, with lower rates of discontinuation due to fewer adverse effects, will play important clinical roles.
Keywords: Myeloproliferative disorder, Interferon alpha, Therapy
Table 1 . Summary of clinical trials of IFNα products in patients with MPN..
Clinical trial | Phase | Characteristics | Patient population | IFN | Comparator | Clinical response (ORR/CHR) | Molecular response (ORR/CMR) | Grade III/IV AE/discontinuation rate | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IFN | Comparator | IFN | Comparator | IFN | Comparator | ||||||||
LOW-PV [41] (abstract) | 2 | Low-risk PV (diagnosed less than 3 yr prior) | PV(N=100) | Ropeg-IFNα-2b | Phlebotomy | 84%/NR | 66%/NR | NR | NR | 6%/NR | 8%/NR | ||
Proud-PV/continuation-PV [40] | 3 | Early stage PV (less than 3 years of previous hydroxyurea treatment) | PV (N=257) | Ropeg-IFNα-2b | Hydroxyurea | NR/43% | NR/46% | 34%/NR | 42%/NR (1 yr f/u) | 43%/8% | 34%/4% | ||
NR/71% | NR/51% | 66%/NR | 27%/NR (3 yr f/u) | ||||||||||
MPD-RC 112 [39] (abstract) | 3 | High risk (Treatment-naïv, hydroxyurea <3 mo) | ET (N=81) | Peg-IFNα-2a | Hydroxyurea | 78.0%/35.4% | 69.8%/37.2% (1 y f/u) | NR | NR | 46.3%/NR | 27.5%/NR | ||
PV (N=87) | 59.6%/28.8% | 40.7%/20.4% (2 y f/u) | |||||||||||
MPD-RC 111 [38] | 2 | High risk (hydroxyurea intolerant or resistant) | ET (N=65) | Peg-IFNα-2a | None | 69.2%/43.1% (ET) | CR patients ( | 30.7%/13.9% | |||||
PV(N=50) | 60%/22% (PV) | ||||||||||||
COMBI [46] | 2 | IFN+JAK inhibitor | PV (N=32) | Peg-IFNα-2a+ruxo-litinib | 31%/9% (PV) | 41%/2% | NR/31% (PV) | ||||||
MF (N=18) | 44%/28% (MF) | NR/39% (MF) |
Abbreviations: AE, adverse event; CHR, complete hematologic response; CMR, complete molecular response; ET, essential thrombocythemia; f/u, follow-up; IFNα, interferon alpha; MF, myelofibrosis; MPN, myeloproliferative neoplasm; NR, not reported; ORR, overall response rate; Peg-IFNα-2a, pegylated interferon alpha-2a; PV, polycythemia vera; Ropeg-IFNα-2b, ropeginterferon alpha-2b..
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