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.

• Authors: Kayleigh R Marx, Caitlin R Rausch, Alexandra R Lovell, Nicholas J Short, Shilpa Paul, Nitin Jain, Jenessa Lee, J Michael Savoy, Farhad Ravandi, Elias Jabbour
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 64 Issue 1 Pg. 79-86 (01 2023) ISSN: 1029-2403 [Electronic] United States
• PMID: 36222579 (Publication Type: Review, Journal Article)

Chemical References

• Antifungal Agents
• ponatinib
• Imidazoles
• Pyridazines
• Protein Kinase Inhibitors

Topics

• Humans
• Antifungal Agents (adverse effects)
• Incidence
• Philadelphia Chromosome
• Imidazoles (adverse effects)
• Pyridazines (adverse effects)
• Drug-Related Side Effects and Adverse Reactions
• Protein Kinase Inhibitors (therapeutic use)