TY - JOUR
T1 - Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study
AU - Tojo, Arinobu
AU - Kyo, Taiichi
AU - Yamamoto, Kazuhito
AU - Nakamae, Hirohisa
AU - Takahashi, Naoto
AU - Kobayashi, Yukio
AU - Tauchi, Tetsuzo
AU - Okamoto, Shinichiro
AU - Miyamura, Koichi
AU - Hatake, Kiyohiko
AU - Iwasaki, Hiromi
AU - Matsumura, Itaru
AU - Usui, Noriko
AU - Naoe, Tomoki
AU - Tugnait, Meera
AU - Narasimhan, Narayana I.
AU - Lustgarten, Stephanie
AU - Farin, Heinrich
AU - Haluska, Frank
AU - Ohyashiki, Kazuma
N1 - Publisher Copyright:
© 2017, The Japanese Society of Hematology.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients; MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%); common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs); no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph+ALL resistant/intolerant to prior TKI treatment; safety data support a recommended starting dose of 45 mg/day in these patients.
AB - In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients; MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%); common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs); no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph+ALL resistant/intolerant to prior TKI treatment; safety data support a recommended starting dose of 45 mg/day in these patients.
KW - CML
KW - Japanese population
KW - Ph+ALL
KW - Phase 1/2
KW - Ponatinib
UR - https://www.scopus.com/pages/publications/85018672492
UR - https://www.scopus.com/pages/publications/85018672492#tab=citedBy
U2 - 10.1007/s12185-017-2238-9
DO - 10.1007/s12185-017-2238-9
M3 - Article
C2 - 28444644
AN - SCOPUS:85018672492
SN - 0925-5710
VL - 106
SP - 385
EP - 397
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 3
ER -