Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea

Abdulraheem Yacoub, John Mascarenhas, Heidi Kosiorek, Josef T. Prchal, Dmitry Berenzon, Maria R. Baer, Ellen Ritchie, Richard T. Silver, Craig Kessler, Elliott Winton, Maria Chiara Finazzi, Alessandro Rambaldi, Alessandro M. Vannucchi, David Leibowitz, Damiano Rondelli, Murat O. Arcasoy, Rosalind Catchatourian, Joseph Vadakara, Vittorio Rosti, Elizabeth HexnerMarina Kremyanskaya, Lonette Sandy, Joseph Tripodi, Vesna Najfeld, Noushin Farnoud, Elli Papaemmanuil, Mohamed Salama, Rona Singer-Weinberg, Raajit Rampal, Judith D. Goldberg, Tiziano Barbui, Ruben Mesa, Amylou C. Dueck, Ronald Hoffman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Prior studies have reported high response rates with recombinant interferon-a (rIFN-a) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-a,we investigated the outcomes of pegylated-rIFN-a2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PVwho were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 monthswere 69.2%(43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P 5 .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was 26% (range, 284%to 47%) in patients achieving a CR vs 14%(range, 218% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU.

Original languageEnglish (US)
Pages (from-to)1498-1509
Number of pages12
JournalBlood
Volume134
Issue number18
DOIs
StatePublished - Oct 31 2019
Externally publishedYes

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Essential Thrombocythemia
Polycythemia Vera
Hydroxyurea
Refractory materials
Interferons
peginterferon alfa-2a
Therapeutics
Myeloproliferative Disorders
Alleles
Research Personnel

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Yacoub, A., Mascarenhas, J., Kosiorek, H., Prchal, J. T., Berenzon, D., Baer, M. R., ... Hoffman, R. (2019). Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood, 134(18), 1498-1509. https://doi.org/10.1182/blood.2019000428

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. / Yacoub, Abdulraheem; Mascarenhas, John; Kosiorek, Heidi; Prchal, Josef T.; Berenzon, Dmitry; Baer, Maria R.; Ritchie, Ellen; Silver, Richard T.; Kessler, Craig; Winton, Elliott; Finazzi, Maria Chiara; Rambaldi, Alessandro; Vannucchi, Alessandro M.; Leibowitz, David; Rondelli, Damiano; Arcasoy, Murat O.; Catchatourian, Rosalind; Vadakara, Joseph; Rosti, Vittorio; Hexner, Elizabeth; Kremyanskaya, Marina; Sandy, Lonette; Tripodi, Joseph; Najfeld, Vesna; Farnoud, Noushin; Papaemmanuil, Elli; Salama, Mohamed; Singer-Weinberg, Rona; Rampal, Raajit; Goldberg, Judith D.; Barbui, Tiziano; Mesa, Ruben; Dueck, Amylou C.; Hoffman, Ronald.

In: Blood, Vol. 134, No. 18, 31.10.2019, p. 1498-1509.

Research output: Contribution to journalArticle

Yacoub, A, Mascarenhas, J, Kosiorek, H, Prchal, JT, Berenzon, D, Baer, MR, Ritchie, E, Silver, RT, Kessler, C, Winton, E, Finazzi, MC, Rambaldi, A, Vannucchi, AM, Leibowitz, D, Rondelli, D, Arcasoy, MO, Catchatourian, R, Vadakara, J, Rosti, V, Hexner, E, Kremyanskaya, M, Sandy, L, Tripodi, J, Najfeld, V, Farnoud, N, Papaemmanuil, E, Salama, M, Singer-Weinberg, R, Rampal, R, Goldberg, JD, Barbui, T, Mesa, R, Dueck, AC & Hoffman, R 2019, 'Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea', Blood, vol. 134, no. 18, pp. 1498-1509. https://doi.org/10.1182/blood.2019000428
Yacoub A, Mascarenhas J, Kosiorek H, Prchal JT, Berenzon D, Baer MR et al. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood. 2019 Oct 31;134(18):1498-1509. https://doi.org/10.1182/blood.2019000428
Yacoub, Abdulraheem ; Mascarenhas, John ; Kosiorek, Heidi ; Prchal, Josef T. ; Berenzon, Dmitry ; Baer, Maria R. ; Ritchie, Ellen ; Silver, Richard T. ; Kessler, Craig ; Winton, Elliott ; Finazzi, Maria Chiara ; Rambaldi, Alessandro ; Vannucchi, Alessandro M. ; Leibowitz, David ; Rondelli, Damiano ; Arcasoy, Murat O. ; Catchatourian, Rosalind ; Vadakara, Joseph ; Rosti, Vittorio ; Hexner, Elizabeth ; Kremyanskaya, Marina ; Sandy, Lonette ; Tripodi, Joseph ; Najfeld, Vesna ; Farnoud, Noushin ; Papaemmanuil, Elli ; Salama, Mohamed ; Singer-Weinberg, Rona ; Rampal, Raajit ; Goldberg, Judith D. ; Barbui, Tiziano ; Mesa, Ruben ; Dueck, Amylou C. ; Hoffman, Ronald. / Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. In: Blood. 2019 ; Vol. 134, No. 18. pp. 1498-1509.
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abstract = "Prior studies have reported high response rates with recombinant interferon-a (rIFN-a) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-a,we investigated the outcomes of pegylated-rIFN-a2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PVwho were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 monthswere 69.2{\%}(43.1{\%} and 26.2{\%}) in ET patients and 60{\%} (22{\%} and 38{\%}) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5{\%} vs 28.0{\%}; P 5 .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was 26{\%} (range, 284{\%}to 47{\%}) in patients achieving a CR vs 14{\%}(range, 218{\%} to 56{\%}) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9{\%} of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU.",
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AU - Yacoub, Abdulraheem

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AU - Kosiorek, Heidi

AU - Prchal, Josef T.

AU - Berenzon, Dmitry

AU - Baer, Maria R.

AU - Ritchie, Ellen

AU - Silver, Richard T.

AU - Kessler, Craig

AU - Winton, Elliott

AU - Finazzi, Maria Chiara

AU - Rambaldi, Alessandro

AU - Vannucchi, Alessandro M.

AU - Leibowitz, David

AU - Rondelli, Damiano

AU - Arcasoy, Murat O.

AU - Catchatourian, Rosalind

AU - Vadakara, Joseph

AU - Rosti, Vittorio

AU - Hexner, Elizabeth

AU - Kremyanskaya, Marina

AU - Sandy, Lonette

AU - Tripodi, Joseph

AU - Najfeld, Vesna

AU - Farnoud, Noushin

AU - Papaemmanuil, Elli

AU - Salama, Mohamed

AU - Singer-Weinberg, Rona

AU - Rampal, Raajit

AU - Goldberg, Judith D.

AU - Barbui, Tiziano

AU - Mesa, Ruben

AU - Dueck, Amylou C.

AU - Hoffman, Ronald

PY - 2019/10/31

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