Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies

• Published in: Annals of hematology Vol. 97; no. 4; pp. 617 - 627
• Main Authors: Kiladjian, Jean-Jacques, Guglielmelli, Paola, Griesshammer, Martin, Saydam, Guray, Masszi, Tamas, Durrant, Simon, Passamonti, Francesco, Jones, Mark, Zhen, Huiling, Li, Jingjin, Gadbaw, Brian, Perez Ronco, Julian, Khan, Mahmudul, Verstovsek, Srdan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2018; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Blood cancer; Bloodletting - adverse effects; Combined Modality Therapy - adverse effects; Cross-Over Studies; Drug Monitoring; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Hematology; Humans; Hydroxyurea - adverse effects; Hydroxyurea - therapeutic use; Inhibitor drugs; Interferons - adverse effects; Interferons - therapeutic use; Janus Kinases - antagonists & inhibitors; Janus Kinases - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Phlebotomy; Polycythemia Vera - drug therapy; Polycythemia Vera - metabolism; Polycythemia Vera - physiopathology; Polycythemia Vera - therapy; Practice Patterns, Physicians; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Reproducibility of Results; Splenomegaly - etiology; Splenomegaly - prevention & control; Studies; Chronic myeloproliferative neoplasms; Ruxolitinib; Polycythemia vera; Interferon
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-017-3225-1

Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy [hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients)] and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at clinicaltrials.gov .