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CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival

Abstract

Interferon-alpha (rIFNα) is the only disease-modifying treatment for polycythemia vera (PV), but whether or not it prolongs survival is unknown. This large single center retrospective study of 470 PV patients compares the myelofibrosis-free survival (MFS) and overall survival (OS) with rIFNα to two other primary treatments, hydroxyurea (HU) and phlebotomy-only (PHL-O). The median age at diagnosis was 54 years (range 20–94) and the median follow-up was 10 years (range 0–45). Two hundred and twenty-nine patients were women (49%) and 208 were high-risk (44%). The primary treatment was rIFNα in 93 (20%), HU in 189 (40%), PHL-O in 133 (28%) and other cytoreductive drugs in 55 (12%). The treatment groups differed by ELN risk score (p < 0.001). In low-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 84%, 65% and 55% respectively (p < 0.001) and 20-year OS was 100%, 85% and 80% respectively (p = 0.44). In high-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 89%, 41% and 36% respectively (p = 0.19) and 20-year OS was 66%, 40%, 14% respectively (p = 0.016). In multivariable analysis, longer time on rIFNα was associated with a lower risk of myelofibrosis (HR: 0.91, p < 0.001) and lower mortality (HR: 0.94, p = 0.012). In conclusion, this study supports treatment of PV with rIFNα to prevent myelofibrosis and potentially prolong survival.

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Fig. 1: Myelofibrosis-free survival (MFS) and overall survival (OS) of PV patients.
Fig. 2: Fibrosis grade MF2-3 over time on treatment.
Fig. 3: Cytoreductive treatment timeline of PV study population ordered by first treatment and its duration.

References

  1. Passamonti F, Giorgino T, Mora B, Guglielmelli P, Rumi E, Maffioli M, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31:2726–31.

    CAS  Article  Google Scholar 

  2. Spivak JL. Myeloproliferative neoplasms. N Engl J Med. 2017;376:2168–81.

    CAS  Article  Google Scholar 

  3. Masarova L, Yin CC, Cortes JE, Konopleva M, Borthakur G, Newberry KJ, et al. Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Exp Hematol Oncol. 2017;6:30.

    Article  Google Scholar 

  4. Silver RT. Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer. 2006;107:451–8.

    CAS  Article  Google Scholar 

  5. Kiladjian J-J, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. 2008;112:3065–72.

    CAS  Article  Google Scholar 

  6. Silver RT, Hasselbalch HC. Optimal therapy for polycythemia vera and essential thrombocythemia: Preferred use of interferon therapy based on phase 2 trials. Hematology. 2016;21:387–91.

    CAS  Article  Google Scholar 

  7. Tashi T, Swierczek S, Kim SJ, Salama ME, Song J, Heikal N, et al. Pegylated interferon Alfa-2a and hydroxyurea in polycythemia vera and essential thrombocythemia: differential cellular and molecular responses. Leukemia. 2018;32:1830–3.

    CAS  Article  Google Scholar 

  8. Sacchi S, Leoni P, Liberati M, Riccardi A, Tabilio A, Tartoni P, et al. A prospective comparison between treatment with phlebotomy alone and with interferon-alpha in patients with polycythemia vera. Ann Hematol. 1994;68:247–50.

    CAS  Article  Google Scholar 

  9. Silver RT, Vandris K, Goldman JJ. Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report. Blood. 2011;117:6669–72.

    CAS  Article  Google Scholar 

  10. Silver RT, Kiladjian JJ, Hasselbalch HC. Interferon and the treatment of polycythemia vera, essential thrombocythemia and myelofibrosis. Expert Rev Hematol. 2013;6:49–58.

    CAS  Article  Google Scholar 

  11. Silver RT, Barel AC, Lascu E, Ritchie EK, Roboz GJ, Christos PJ, et al. The effect of initial molecular profile on response to recombinant interferon-α (rIFNα) treatment in early myelofibrosis. Cancer. 2017;123:2680–7.

    CAS  Article  Google Scholar 

  12. Bose P, Deininger MW, Dunbar A, George T, Gojo I, Gundabolu K et al. NCCN Guidelines Panel Disclosures NCCN Guidelines Version 1.2020 Myeloproliferative Neoplasms. 2020.

  13. Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European. LeukemiaNet Leuk. 2018;32:1057–69.

    Article  Google Scholar 

  14. Knudsen TA, Hansen DL, Ocias LF, Bjerrum OW, Brabrand M, El Fassi D, et al. Long-term efficacy and safety of recombinant interferon alpha-2 vs. hydroxyurea in polycythemia vera: preliminary results from the three-year analysis of the Daliah trial - a randomized controlled phase III clinical trial. Blood. 2018;132:580.

    Article  Google Scholar 

  15. Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7:e196–208.

    Article  Google Scholar 

  16. Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, et al. Results of the Myeloproliferative Neoplasms - Research Consortium (MPN-RC) 112 Randomized Trial of Pegylated Interferon Alfa-2a (PEG) Versus Hydroxyurea (HU) Therapy for the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET). Blood. 2018;132:577.

    Article  Google Scholar 

  17. Berlin NI. Diagnosis and classification of the polycythemias. Semin Hematol. 1975;12:339–51.

    CAS  PubMed  Google Scholar 

  18. Silver RT, Chow W, Orazi A, Arles SP, Goldsmith SJ. Evaluation of WHO criteria for diagnosis of polycythemia vera: a prospective analysis. Blood. 2013;122:1881–6.

    CAS  Article  Google Scholar 

  19. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    CAS  Article  Google Scholar 

  20. Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, et al. Cardiovascular Events and Intensity of Treatment in Polycythemia Vera. N. Engl J Med. 2013;368:22–33.

    CAS  Article  Google Scholar 

  21. Cancer Institute N. Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017 https://www.meddra.org/ (Accessed 18 May 2019).

  22. Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment. Leukemia. 2008;22:437–438.

    CAS  Article  Google Scholar 

  23. Barbui T, Vannucchi AM, De Stefano V, Masciulli A, Carobbio A, Ghirardi A et al. Phase II randomized clinical trial comparing ropeginterferon versus phlebotomy in low-risk patients with polycythemia vera. results of the pre-planned interim analysis. Hematologica; 303391; LB. https://library.ehaweb.org/eha/2020/eha25th/303391/tiziano.barbui.phase.ii.randomized.clinical.trial.comparing.ropeginterferon.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dlb2602 (Accessed 5 Jul 2020).

  24. Hasselbalch HC, Silver RT. Interferon in polycythemia vera and related neoplasms. Can it become the treatment of choice without a randomized trial? Expert Rev Hematol. 2015;8:439–45.

    CAS  Article  Google Scholar 

  25. Verstovsek S, Silver RT, Cross NCP, Tefferi A. JAK2V617F mutational frequency in polycythemia vera: 100%, >90%, less? Leukemia. 2006;20:2067.

    CAS  Article  Google Scholar 

  26. Wang YL, Vandris K, Jones A, Cross NCP, Christos P, Adriano F, et al. JAK2 Mutations are present in all cases of polycythemia vera. Leukemia 2008;22:1289.

    CAS  Article  Google Scholar 

  27. Silver RT. Recombinant interferon-alpha for treatment of polycythaemia vera. Lancet (Lond, Engl). 1988;2:403.

    CAS  Article  Google Scholar 

  28. Silver RT. Interferon-α2b: A new treatment for polycythemia vera. Ann Intern Med. 1993;119:1091–2.

    CAS  Article  Google Scholar 

  29. Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European leukemiaNet. J Clin Oncol. 2011;29:761–70.

    Article  Google Scholar 

  30. Srour SA, Devesa SS, Morton LM, Check DP, Curtis RE, Linet MS, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-12. Br J Haematol. 2016;174:382–96.

    CAS  Article  Google Scholar 

  31. Szuber N, Vallapureddy RR, Penna D, Lasho TL, Finke C, Hanson CA, et al. Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger. Am J Hematol. 2018;93:1474–84.

    CAS  Article  Google Scholar 

  32. Karantanos T, Chaturvedi S, Braunstein EM, Spivak J, Resar L, Karanika S, et al. Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden. Blood Adv. 2020;4:2567–76.

    Article  Google Scholar 

  33. Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23:2224–32.

    Article  Google Scholar 

  34. Alvarez-Larr an A, Kerguelen A, Hern andez-Boluda JC, erez-Encinas MP, Ferrer-Mar ın F, arez AB, et al. Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br J Haematol. 2016;172:786–93.

    CAS  Article  Google Scholar 

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Acknowledgements

We acknowledge Paul J Christos, PhD for his review of the statistical methodology and results.

This study was supported by grants from the David L. Johns Family of the Cancer Research & Treatment Fund (CR&T), the Myeloproliferative Neoplasms Research Foundation (MPN-RF), the Clinical & Translational Science Center (CTSC) of Weill Cornell and the National Center for Advancing Translational Sciences (NCATS) (grant # 1 UL1 TR002384-04).

Data sharing statement

Data will not be publicly available due to HIPAA regulations. Similarly, individual patient data will not be shared. However, a request for sharing de-identified data can be made to the corresponding author and approval will be sought from the IRB.

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Contributions

GAZ – designed the study, collected data, analyzed data, examined patients and wrote the paper. SK – collected data, extracted data and analyzed data. TC, GH, DJ, NS, CS – collected data. EKR – examined patients and reviewed manuscript. JMS – conceived and designed the study, examined patients, and reviewed manuscript. RTS – conceived and designed the study, examined patients and wrote the paper. All authors approved final manuscript.

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Correspondence to Richard T. Silver.

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Conflict of interest

GAZ – Consultancy, PharmaEssentia. SK, TC, GH, DJ, NS, CS, EKR, and JMS – No conflicts of interest to disclose. RTS – Speaker bureau and consultancy, PharmaEssentia.

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Presented in part at the annual meetings of the American Society of Hematology in Atlanta, GA, 2018; Orlando, FL, 2019, and San Diego, CA, 2020.

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Abu-Zeinah, G., Krichevsky, S., Cruz, T. et al. Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival. Leukemia 35, 2592–2601 (2021). https://doi.org/10.1038/s41375-021-01183-8

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