Incidence of adverse effects in patients receiving ponatinib with concomitant azole antifungals

Abstract

Ponatinib plus Hyper-CVAD yields a five-year overall survival of 73% in patients with Philadelphia-positive acute lymphoblastic leukemia. Ponatinib dose intensity is associated with increased incidence of adverse effects (AEs), including vascular events. Ponatinib combined with azole antifungals may further increase the risk of AEs due to increased ponatinib exposure. We reviewed 53 patients who received ponatinib with intensive (n = 39; 74%) or low-intensity chemotherapy (n = 14; 26%). Forty-eight patients (91%) received concomitant azole. Ponatinib was commonly initiated at 30 mg (n = 30; 57%) or 45 mg daily (n = 21; 40%). Twenty-six patients (49%) experienced at least one grade ≥3 AE possibly related to ponatinib; 19 (73%) were receiving a ponatinib dose equivalent ≥30mg and 58% >45mg. Eight patients (15%) experienced 10 vascular events, including 1 arterial event; 9 occurred on a ponatinib dose equivalent ≥30mg and 5 occurred while on an azole. Vascular events pose a clinical challenge with the risk potentially increasing with concomitant azoles.

Keywords:

• Ponatinib
• ponatinib adverse events
• ponatinib and azoles

Disclosure statement

Kayleigh R. Marx: none, Caitlin R. Rausch: none, Alexandra R. Lovell: none, Nicholas J. Short: Research grants from Takeda Oncology, Shilpa Paul: none, Nitin Jain: Research Funding from Pharmacyclics, AbbVie, Genentech, AstraZeneca, BMS, Pfizer, Servier, ADC Therapeutics, Cellectis, Adaptive Biotechnologies, Incyte, Precision Biosciences, Aprea Therapeutics, Fate Therapeutics, Mingsight, Takeda, Medisix, Loxo Oncology, Novalgen, Dialectic Therapeutics, TransThera Sciences. Advisory Board/Honoraria from Pharmacyclics, Janssen, AbbVie, Genentech, AstraZeneca, BMS, Servier, Adaptive Biotechnologies, Precision Biosciences, Beigene, Cellectis, TG Therapeutics, ADC Therapeutics, MEI Pharma, Ipsen, CareDX, Jenessa Lee: none, J. Michael Savoy: none, Farhad Ravandi: none, Elias Jabbour: Research grants and consultancy from Abbvie, adapative biotechnologies, Pfizer, Amgen, BMS, Novartis, Takeda, Genentech