TY - JOUR
T1 - Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies
AU - Kiladjian, Jean Jacques
AU - Guglielmelli, Paola
AU - Griesshammer, Martin
AU - Saydam, Guray
AU - Masszi, Tamas
AU - Durrant, Simon
AU - Passamonti, Francesco
AU - Jones, Mark
AU - Zhen, Huiling
AU - Li, Jingjin
AU - Gadbaw, Brian
AU - Perez Ronco, Julian
AU - Khan, Mahmudul
AU - Verstovsek, Srdan
N1 - Funding Information:
Conflict of interest JJK reports grants and personal fees from Novartis, grants and personal fees from AOP Orphan, during the conduct of the study; personal fees from Shire, outside the submitted work. PG has nothing to disclose. MG participated in speaker bureau and advisory boards for Novartis, Shire, and AOP Orphan, outside the submitted work. GS received research funding from Novartis, participated in speaker bureau for Novartis, and received honoraria from Novartis, Celgene, Bristol-Myers Squibb, and Gilead, outside the submitted work. TM served as a consultant for Takeda, Novartis, Bristol-Myers Squibb, and Janssen Cilag, outside the submitted work. SD has nothing to disclose. FP participated in speaker bureau and advisory board for Novartis. MJ and HZ are employees of Incyte Corporation and own stocks of company. JL, BG, JPR, and MK are employees of Novartis. JL, MK and BG own stocks of company. SV participated in advisory boards for Novartis and Incyte. Ethics approval and consent to participate This study was approved by the institutional review board (IRB). Each investigator site IRB approved the respective protocols. Informed consent was obtained from all patients for being included in the study.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - Chronic myeloproliferative neoplasms
KW - Interferon
KW - Polycythemia vera
KW - Ruxolitinib
UR - http://www.scopus.com/inward/record.url?scp=85042733285&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042733285&partnerID=8YFLogxK
U2 - 10.1007/s00277-017-3225-1
DO - 10.1007/s00277-017-3225-1
M3 - Article
C2 - 29396713
AN - SCOPUS:85042733285
SN - 0939-5555
VL - 97
SP - 617
EP - 627
JO - Annals of Hematology
JF - Annals of Hematology
IS - 4
ER -