Citation: British Journal of Haematology. 2019, 185, 192-93
Author: Schofield J.; Knight K.; Salim R.; Patel A.
Abstract: Ponatinib is indicated for Philadelphia (Ph+) chromosome associated leukaemia (chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL)), including patients with a T315I mutation or advanced phase disease.1 Ponatinib is subject to additional monitoring requirements due to a significant risk of vascular occlusive events. High rates of arterial (25%) and venous (6%) thrombotic events contribute to significant morbidity and treatment interruption. 1 Apixaban prophylaxis is indicated for both arterial and venous thrombosis in patients with cancer.2 Most patients prefer oral rather than subcutaneous anti-thrombotic prophylaxis. We are unaware of published or pharmaceutical data regarding the feasibility, safety and efficacy of concurrent apixaban use with ponatinib, given their potential interaction. Our primary study objective to was to assess the feasibility of this combination, and our secondary objective was to assess safety and efficacy. This retrospective study identified and included all patients with CML or Ph+ ALL that preferred oral (instead of subcutaneous) antithrombotic prophylaxis, and that who commenced on ponatinib with apixaban. Data were collected and analysed from patients treated at our regional UK centre during 2017-2018. Relevant information on patient characteristics, BCR-ABL1 transcript levels (efficacy measure), and the development of thrombotic and bleeding events was identified. Relevant adverse events, bleeding, and thrombotic events were used to measure safety, and were classified using criteria from the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Bleeding was also assessed using the World Health Organisation (WHO) bleeding scale for cancer.3 Major bleeding was assessed using the International Society on Thrombosis and Haemostasis (ISTH) criteria.2 The study was conducted in accordance with the Ethical Principles for Medical Research Involving Human Subjects outlined in the Declaration of Helsinki. Five patients with CML were commenced on combination ponatinib and apixaban therapy (Table). Two patients had a T315I mutation and three were in accelerated phase. Median age was 43 years (range 26 to 66 years). No patients had a history of thrombosis prior to treatment. The median duration of treatment was 4 months (range 1 to 9 months). Two patients recommenced combination therapy post-allogeneic stem cell transplantation. There were no arterial or venous thromboembolic or bleeding (including gastrointestinal) events observed after 24 months combination therapy exposure, by CTCAE, WHO, and ISTH criteria. There were no other relevant treatment emergent adverse events attributable to the ponatinib and apixaban combination. Our experience demonstrates the feasibly of concurrent ponatinib and apixaban therapy, including in the post-allogeneic stem cell transplant setting. This approach might be safe and efficacious but our observations should serve as a basis for a larger confirmatory clinical trial.
