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. 2024 Aug 14;54(8):930-938.
doi: 10.1093/jjco/hyae061.

Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan

Naoto Takahashi  1 , Takeshi Kondo  2 , Yuji Ikari  3 , Yoshihiro Fukumoto  4 , Kiyohiko Hatake  5 , Akira Masunari  6 , Seiji Nishibayashi  6 , Akiko Kageyama  6 , Yasuhiko Fukuta  6 , Arinobu Tojo  7
Affiliations

Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan

Naoto Takahashi et al. Jpn J Clin Oncol. .

Abstract

Background: In September 2016, ponatinib was approved in Japan for the treatment of patients with chronic myeloid leukemia with resistance/intolerance to prior tyrosine kinase inhibitors and patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

Methods: We conducted a post-marketing all-case surveillance to study the safety and efficacy of ponatinib in clinical practice, focusing on arterial occlusive events.

Results: Data from 724 patients were collected for 2 years from the initiation of ponatinib. The arterial occlusive events were reported in 6.49% (47/724) with an exposure-adjusted incidence rate of 6.8/100 person-years. The risks associated with arterial occlusive events were age and comorbidities including hypertension and diabetes. At 104 weeks, the cumulative major molecular response rate in patients with chronic-phase chronic myeloid leukemia was 67.2% and the complete cytogenetic response in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was 80.0%. Furthermore, the estimated 1-year overall survival rate was 98.5% for chronic-phase chronic myeloid leukemia and 68.6% for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Conclusions: This surveillance demonstrated that ponatinib has a favorable safety and efficacy profile in Japanese patients and also showed the necessity of closely monitoring arterial occlusive events in older adults and patients with predisposing factors for atherosclerosis.

Keywords: acute lymphoblastic leukemia; arterial occlusive events; chronic myeloid leukemia; ponatinib; post-marketing surveillance.

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Conflict of interest statement

Naoto Takahashi has received all support for the present manuscript from Otsuka Pharmaceutical; honoraria from Pfizer, Novartis and Otsuka Pharmaceutical; Kiyohiko Hatake has received all support for the present manuscript from Otsuka Pharmaceutical; consuling fee from Meiji Seika Pharmaceutical; honoraria from Takeda Pharmaceutical, Celgene Corporation, Eisai, Meiji Seika Pharmaceutical, Chugai Pharmaceutical, towa pharmaceutical, Daiichi Sankyo and Yakult Headquarters; Yuji Ikari has received all support for the present manuscript from Otsuka Pharmaceutical; honoraria from Abbott Medical Japan, Amgen, Japan,Boehringerheim, Bayer Pharmaceuticals, AstraZeneca, Daiichi Sankyo and Novartis; leaderchip or fiduciancy role in other board, survey, committee or advocary group, paid or unpaid; from Japanese circulation society, Japnanese association of caridiovacular intervention and therapeutics; Takeshi Kondo has received all support for the present manuscript from Otsuka Pharmaceutical; grants or contracts from any entity from Pfizer Health Research Foundation; honoraria from Astellas Pharma, Pfizer, Nippon Sinyaku, Eisai, Novartis, Abbvie, Meiji Seika Pharma, Bristol Meyers Squibb, Asahi Kasei Pharma and Otsuka Pharmaceutical; Yushihiro Fukumoto has received all support for the present manuscript from Otsuka Pharmaceutical; grants or contracts from any entity from Alnylam Pharmaceuticals, Janssen Pharmaceutical, lonis Pharmaceutical INC, Japan Medical Device Technology, Bayer Pharmaceuticals, Teijin Pharma, Japan Lifeline and Abbott Medical Japan; honoraria from AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, Japan,Boehringerheim, Bayel Pharmaceutical, Otsuka Pharmaceutical, Kowa, Toaeiyo, Novartis and Janssen Pharmaceutical; Arinob Tojo have received all support for the present manuscript from Otsuka Pharmaceutical; grants or contracts from any entity from KM Biologics and Sysmex; consulting fee from Sysmex and LSI medicine; honoraria from Otsuka Pharmaceutical, Novartis and Bristol Meyer Squib.Akira Masunari, Seiji Nishibayashi, Akiko Kageyama and Yasuhiko Fukuta are employees of Otsuka Pharmaceutical.

Figures

Figure 1
Figure 1
Cumulative incidence rates of arterial occlusive events in patients with CML-CP and Ph+ ALL. The cumulative incidence rates of cerebrovascular (Solid line), cardiovascular (Dotted line), and peripheral arterial events (Dashed line) are shown in patients with CML-CP (A) and Ph+ ALL (B). Incidence rates are labeled at years 1 and 2. CML, chronic myeloid leukemia; CP, chronic-phase; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia.
Figure 2
Figure 2
Cumulative molecular response rates in patients with CML-CP who were not achieved major molecular response (MMR) to prior treatment. The cumulative MMR rate, MR4.0 rate and MR4.5 rate in patients with CML-CP patients who did not achieve MMR before treatment with ponatinib are shown. Response rates are labeled at weeks 12, 24, 52, and 104. CML, chronic myeloid leukemia; CP, chronic-phase; IS, international standard; MMR, major molecular response (BCR::ABL1 transcripts [IS] ≤ 0.1%); MR4.0, molecular response with a 4.0-log reduction (BCR::ABL1 transcripts [IS] ≤ 0.01%); MR4.5, molecular response with a 4.5-log reduction (BCR::ABL1 transcripts [IS] ≤ 0.0032%).
Figure 3
Figure 3
Complete and partial cytogenetic response rates in patients with Ph+ ALL. The complete cytogenetic response rate (Solid) and partial cytogenetic response rate (Dotted) before and after initiating ponatinib treatment in patients with Ph+ ALL are shown. CCyR, complete cytogenetic response; PCyR, partial cytogenetic response; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia.
See this image and copyright information in PMC

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