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

• Published in: Blood Vol. 134; no. 18; pp. 1498 - 1509
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.10.2019; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Clinical Trials and Observations; Drug Resistance, Neoplasm - drug effects; Female; Humans; Hydroxyurea; Interferon-alpha - therapeutic use; Male; Middle Aged; Polycythemia Vera - drug therapy; Polyethylene Glycols - therapeutic use; Recombinant Proteins - therapeutic use; Thrombocythemia, Essential - drug therapy; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2019000428

Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (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 PV who 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 months were 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 = .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was −6% (range, −84% to 47%) in patients achieving a CR vs +4% (range, −18% 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. This trial was registered at www.clinicaltrials.gov as #NCT01259856. •Pegylated-rIFN-α2a can achieve an ORR of 69% and 60% in ET and PV patients, respectively, previously treated with hydroxyurea.•The presence of a CALR mutation was associated with superior CR rates in ET patients treated with pegylated-rIFN-α2a. [Display omitted]