Ponatinib for the treatment of adult patients with resistant or intolerant Chronic-Phase Chronic Myeloid Leukemia

ABSTRACT

Introduction

Patients with chronic myeloid leukemia in chronic phase (CP-CML) who are resistant or intolerant to second-generation tyrosine kinase inhibitors (TKIs) may benefit from treatment with a third-generation TKI, like ponatinib.

Areas covered

In this review, the authors discuss the role of ponatinib, an oral pan-inhibitor of BCR-ABL1, with potent activity in heavily pretreated patients, including T315I mutation. In the long-term follow-up of the PACE trial, 60% of patients with prior TKIs exposure achieved a major cytogenetic response with ponatinib and 40% a major molecular response; 5-year overall survival was 73%. Cardiovascular adverse events represent the major toxicity associated with ponatinib. Adopting a dose-reduction approach appeared to be safe: starting with 45 or 30 mg and decreasing to 15 mg once BCR-ABL1/ABL1≤1% is achieved. In patients who are not candidates for ponatinib therapy, asciminib or other novel TKIs like HQP1351, represent alternative options.

Expert opinion

In patients with CP-CML resistant or intolerant to second-generation TKIs, we favor using a third-generation TKI such as ponatinib. Although we initiate a donor search as soon as a patient fails a second-generation TKI, we still prefer treating patients with ponatinib and will only consider transplantation in the event of no response or disease progression.

KEYWORDS:

• Chronic myeloid leukemia
• intolerance
• ponatinib
• resistance
• second line
• third line
• tyrosine kinase inhibitors

Declaration of interest

GC Issa has received research funding from Celgene, Kura Oncology, Syndax and Novartis, and consultancy fees from Novartis and Kura Oncology. E Jabbour has received research grants from AbbVie, Adaptive Biotechnologies, Amgen, Pfizer, and Takeda, as well as consultancy fees from AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Genentech, Incyte, Novartis, Pfizer, and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.