TY - JOUR
T1 - Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea
AU - Yacoub, Abdulraheem
AU - Mascarenhas, John
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
N1 - Funding Information:
Conflict-of-interest disclosure: A.Y. reports consultation and speaker honoraria for Incyte, Seattle Genetics, and Novartis. J.M. reports clinical trial research support paid to the institution from Incyte, Roche, Novartis, CTI Biopharma, Janssen, Merck, Promedior, and Celgene and membership on the clinical trial steering committee and advisory boards of Roche, CTI Biopharma, Incyte, and Celgene. J.T.P. reports clinical trial research support paid to the institution from Incyte, Abbvie, Pharmaessentia, and consulting honoraria from Agios. M.R.B. reports clinical trial research support paid to the institution from Abbvie, AI, Astellas, Forma, Incyte, Kite, and Takeda. E.W. reports serving on the advisory boards of Incyte Corporation and Gilead Sciences. A.R. reports consultation and speaker honoraria from Novartis, Amgen, Roche, Celgene, and Italfarmaco. A.M.V. reports speaker honoraria from Novartis and Celgene and fees from Novartis, CTI, Celgene for participation on advisory boards. D.R. reports consulting honoraria from Incyte. M.A. reports research grant support paid to the institution from Incyte, CTI Biopharma, Samus Therapeutics, Janssen, and Gilead. R.T.S. reports consultancy and speaker bureau for Pharmaessentia. R.R. has received consulting fees from Stemline, Celgene, Agios Pharmaceuticals, Apexx Oncology, Beyond Spring, Partner Therapeutics, and Jazz Pharmaceuticals and has received research funding from Constellation Pharmaceuticals, Incyte, and Stemline Therapeutics. R.M. reports research support from Incyte, Genetech, CTI, Promedior, and Abbvie and consulting for Novartis, Sierra Oncology, and La Jolla Pharma. R.H. reports research support from Roche. The remaining authors declare no competing financial interests.
Funding Information:
1Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS; 2Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; 3Mayo Clinic, Scottsdale, AZ; 4Division of Hematology, University of Utah School of Medicine and 5Huntsman Cancer Center, Salt Lake City, UT; 6Comprehensive Cancer Center, Wake Forest University Medical Center, Wake Forest Health, Winston-Salem, NC; 7Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD; 8Division of Hematology and Oncology, Department of Medicine, Richard T. Silver Myeloproliferative Neoplasms Center, Weill Cornell Medical College, New York, NY; 9Georgetown University Medical Center, Washington, DC; 10Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; 11Department of Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy; 12Department of Oncology, University of Milan, Ospedale Papa Giovanni XXIII, Bergamo, Italy; 13Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, and 14Denothe Excellence Center, University of Florence, Florence, Italy; 15Department of Oncology, Palo Alto Medical Foundation, Sutter Health, Palo Alto, CA; 16Division of Hematology and Oncology, University of Illinois, Chicago, IL; 17Division of Hematology, Duke University School of Medicine, Durham, NC; 18Department of Oncology, John H. Stroger Jr. Hospital of Cook County, Chicago, IL; 19Geisinger Medical Center, Danville, PA; 20Laboratory of Biochemistry, Biotechnology, and Advanced Diagnosis, Center for the Study of Myelofibrosis, Istituto Di Ricovero e Cura a Carattere Scientifico, Foundation Policlinico San Matteo, Pavia, Italy; 21Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; 22Department of Pathology and 23Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; 24Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY; 25Computational Oncology, 26Center for Hematological Malignancies, and 27Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; 28Mayo Clinic Laboratories, Rochester, MN; 29New York Blood Center, New York, NY; 30Department of Population Health and 31Department of Environmental Medicine, New York University School of Medicine, New York, NY; 32Ospedali Riuniti, Bergamo, Italy; and 33UT Health San Antonio Cancer Center, San Antonio, TX
Funding Information:
This research was made possible by a grant from the National Cancer Institute (NCI), National Institutes of Health (MPN Research Consortium Grant 5P01CA108671-09), an NCI Cancer Center Support Grant/Core Grant to Memorial Sloan Kettering Cancer Center (P30CA008748), and generous independent, unrestricted support from Roche Genentech. R.H. is supported by NCI grant 1K08CA188529-01.
Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019/10/31
Y1 - 2019/10/31
N2 - 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.
AB - 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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U2 - 10.1182/blood.2019000428
DO - 10.1182/blood.2019000428
M3 - Article
C2 - 31515250
AN - SCOPUS:85074499705
SN - 0006-4971
VL - 134
SP - 1498
EP - 1509
JO - Blood
JF - Blood
IS - 18
ER -