Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study

被引：35

作者：

Tojo, Arinobu ^{[1
]}

Kyo, Taiichi ^{[2
,3
]}

Yamamoto, Kazuhito ^{[4
]}

Nakamae, Hirohisa ^{[5
]}

Takahashi, Naoto ^{[6
]}

Kobayashi, Yukio ^{[7
]}

Tauchi, Tetsuzo ^{[8
]}

Okamoto, Shinichiro ^{[9
]}

Miyamura, Koichi ^{[10
]}

Hatake, Kiyohiko ^{[11
]}

Iwasaki, Hiromi ^{[12
]}

Matsumura, Itaru ^{[13
]}

Usui, Noriko ^{[14
]}

Naoe, Tomoki ^{[15
]}

Tugnait, Meera ^{[16
]}

Narasimhan, Narayana I. ^{[16
]}

Lustgarten, Stephanie ^{[16
]}

Farin, Heinrich ^{[16
]}

Haluska, Frank ^{[16
,17
]}

Ohyashiki, Kazuma ^{[8
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan

[2] Hiroshima Red Cross Hosp, Hiroshima, Japan

[3] Atomic Bomb Survivors Hosp, Hiroshima, Japan

[4] Aichi Canc Ctr Hosp, Nagoya, Aichi, Japan

[5] Osaka City Univ Hosp, Osaka, Japan

[6] Akita Univ Hosp, Akita, Japan

[7] Natl Canc Ctr, Tokyo, Japan

[8] Tokyo Med Univ Hosp, Tokyo, Japan

[9] Keio Univ Hosp, Tokyo, Japan

[10] Japan Red Cross Nagoya Daiichi Hosp, Nagoya, Aichi, Japan

[11] Canc Inst Hosp Japanese Fdn Canc Res, Tokyo, Japan

[12] Kyushu Univ Hosp, Fukuok, Japan

[13] Kinki Univ Hosp, Osaka, Japan

[14] Jikei Univ, Daisan Hosp, Tokyo, Japan

[15] Natl Hosp Org Nagoya Med Ctr, Nagoya, Aichi, Japan

[16] ARIAD Pharmaceut Inc, Cambridge, MA USA

[17] BioCancell Therapeut Ltd, Jerusalem, Israel

来源：

INTERNATIONAL JOURNAL OF HEMATOLOGY | 2017年 / 106卷 / 03期

关键词：

Ponatinib; CML; Japanese population; Ph plus ALL; Phase; 1/2; CHRONIC MYELOID-LEUKEMIA; HEALTHY-SUBJECTS; IMATINIB; PHARMACOKINETICS; DASATINIB; SAFETY; RESISTANCE; BOSUTINIB; AP24534; TRIAL;

D O I：

10.1007/s12185-017-2238-9

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 ae<yen>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.

引用

页码：385 / 397

页数：13

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