Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis. / Mikkelsen, Stine Ulrik; Kjaer, Lasse; Bjørn, Mads Emil; Knudsen, Trine Alma; Sørensen, Anders Lindholm; Andersen, Christen Bertel Lykkegaard; Bjerrum, Ole Weis; Brochmann, Nana; Fassi, Daniel El; Kruse, Torben A; Larsen, Thomas Stauffer; Mourits-Andersen, Hans Torben; Nielsen, Claus Henrik; Pallisgaard, Niels; Thomassen, Mads; Skov, Vibe; Hasselbalch, Hans Carl.

I: Cancer Medicine, Bind 7, Nr. 8, 08.2018, s. 3571-3581.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Mikkelsen, SU, Kjaer, L, Bjørn, ME, Knudsen, TA, Sørensen, AL, Andersen, CBL, Bjerrum, OW, Brochmann, N, Fassi, DE, Kruse, TA, Larsen, TS, Mourits-Andersen, HT, Nielsen, CH, Pallisgaard, N, Thomassen, M, Skov, V & Hasselbalch, HC 2018, 'Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis', Cancer Medicine, bind 7, nr. 8, s. 3571-3581. https://doi.org/10.1002/cam4.1619

APA

Mikkelsen, S. U., Kjaer, L., Bjørn, M. E., Knudsen, T. A., Sørensen, A. L., Andersen, C. B. L., Bjerrum, O. W., Brochmann, N., Fassi, D. E., Kruse, T. A., Larsen, T. S., Mourits-Andersen, H. T., Nielsen, C. H., Pallisgaard, N., Thomassen, M., Skov, V., & Hasselbalch, H. C. (2018). Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis. Cancer Medicine, 7(8), 3571-3581. https://doi.org/10.1002/cam4.1619

Vancouver

Mikkelsen SU, Kjaer L, Bjørn ME, Knudsen TA, Sørensen AL, Andersen CBL o.a. Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis. Cancer Medicine. 2018 aug;7(8):3571-3581. https://doi.org/10.1002/cam4.1619

Author

Mikkelsen, Stine Ulrik ; Kjaer, Lasse ; Bjørn, Mads Emil ; Knudsen, Trine Alma ; Sørensen, Anders Lindholm ; Andersen, Christen Bertel Lykkegaard ; Bjerrum, Ole Weis ; Brochmann, Nana ; Fassi, Daniel El ; Kruse, Torben A ; Larsen, Thomas Stauffer ; Mourits-Andersen, Hans Torben ; Nielsen, Claus Henrik ; Pallisgaard, Niels ; Thomassen, Mads ; Skov, Vibe ; Hasselbalch, Hans Carl. / Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis. I: Cancer Medicine. 2018 ; Bind 7, Nr. 8. s. 3571-3581.

Bibtex

@article{facb846179634022b1e925c03bae2e0b,
title = "Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis",
abstract = "Interferon-α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation-mediated toxicity, leading to treatment discontinuation in 10-30% of patients. Ruxolitinib, a potent anti-inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon-α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon-α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low-/intermediate-1-risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon-α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow-up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty-seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon-α2 and ruxolitinib is efficacious in patients with low-/intermediate-1-risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.",
author = "Mikkelsen, {Stine Ulrik} and Lasse Kjaer and Bj{\o}rn, {Mads Emil} and Knudsen, {Trine Alma} and S{\o}rensen, {Anders Lindholm} and Andersen, {Christen Bertel Lykkegaard} and Bjerrum, {Ole Weis} and Nana Brochmann and Fassi, {Daniel El} and Kruse, {Torben A} and Larsen, {Thomas Stauffer} and Mourits-Andersen, {Hans Torben} and Nielsen, {Claus Henrik} and Niels Pallisgaard and Mads Thomassen and Vibe Skov and Hasselbalch, {Hans Carl}",
note = "{\textcopyright} 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2018",
month = aug,
doi = "10.1002/cam4.1619",
language = "English",
volume = "7",
pages = "3571--3581",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "JohnWiley & Sons Ltd",
number = "8",

}

RIS

TY - JOUR

T1 - Safety and efficacy of combination therapy of interferon-α2 and ruxolitinib in polycythemia vera and myelofibrosis

AU - Mikkelsen, Stine Ulrik

AU - Kjaer, Lasse

AU - Bjørn, Mads Emil

AU - Knudsen, Trine Alma

AU - Sørensen, Anders Lindholm

AU - Andersen, Christen Bertel Lykkegaard

AU - Bjerrum, Ole Weis

AU - Brochmann, Nana

AU - Fassi, Daniel El

AU - Kruse, Torben A

AU - Larsen, Thomas Stauffer

AU - Mourits-Andersen, Hans Torben

AU - Nielsen, Claus Henrik

AU - Pallisgaard, Niels

AU - Thomassen, Mads

AU - Skov, Vibe

AU - Hasselbalch, Hans Carl

N1 - © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2018/8

Y1 - 2018/8

N2 - Interferon-α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation-mediated toxicity, leading to treatment discontinuation in 10-30% of patients. Ruxolitinib, a potent anti-inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon-α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon-α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low-/intermediate-1-risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon-α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow-up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty-seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon-α2 and ruxolitinib is efficacious in patients with low-/intermediate-1-risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.

AB - Interferon-α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation-mediated toxicity, leading to treatment discontinuation in 10-30% of patients. Ruxolitinib, a potent anti-inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon-α2 as well. We report the preliminary results from a phase II study of CT with pegylated interferon-α2 and ruxolitinib in 50 MPN patients (PV, n = 32; low-/intermediate-1-risk MF, n = 18), the majority (n = 47) being resistant and/or intolerant to interferon-α2 monotherapy. Objectives included remission (2013 revised criteria encompassing histologic, hematologic, and clinical responses), complete hematologic response (CHR), molecular response, and toxicity. Follow-up was 12 months. Partial remission (PR) and sustained CHR were achieved in 9% and 44% of PV patients, respectively. In MF patients, complete or partial remission was achieved in 39%, and sustained CHR in 58%. The median JAK2V617F allele burden declined significantly in both groups. Hematologic toxicity was the most common adverse event and was managed by dose reduction. Thirty-seven serious adverse events were recorded in 23 patients; the discontinuation rate was 20%. We conclude that CT with interferon-α2 and ruxolitinib is efficacious in patients with low-/intermediate-1-risk MF and, to a lesser extent, in patients with PV. These preliminary results encourage phase III studies as well as a study with CT in newly diagnosed MPN patients.

U2 - 10.1002/cam4.1619

DO - 10.1002/cam4.1619

M3 - Journal article

C2 - 29932310

VL - 7

SP - 3571

EP - 3581

JO - Cancer Medicine

JF - Cancer Medicine

SN - 2045-7634

IS - 8

ER -

ID: 218399655