Characterization of adverse cutaneous effects in the setting of ponatinib, bosutinib, andasciminib for chronic myeloid leukemia patients

BCR-ABL tyrosine kinase inhibitors (TKIs) are used in the treatment of chronic myeloid leukemia (CML) and include second- and third-generation agents: ponatinib, bosutinib, and asciminib. While cutaneous adverse events (cAEs) of first-generation TKIs such as imatinib are well-documented, real-world reports involving newer agents remain limited and poorly described. We therefore aimed to characterize the range of cAEs in patients with CML receiving ponatinib, bosutinib, or asciminib. We conducted a retrospective chart review queried from the Research Patient Data Registry of Mass General Brigham from 1979 to 2024. We excluded patients without CML or medication use. 291 patients met inclusion criteria, with 92 (32.3%) receiving ponatinib, 182 (62.5%) receiving bosutinib, and 111 (38.1%) receiving asciminib. 37 (12.7%) patients developed a documented cAE, with 1 patient developing 2 different cAEs. There were 38 total discrete cAEs, including rashes (cAEs=38), pruritus (cAEs=20), xerosis (cAEs=5), hyperpigmentation (cAEs=2) and squamous cell carcinoma (SCC) (cAEs=1). All drugs resulted in acneiform eruptions and maculopapular or papular eruptions. Ponatinib also induced pityriasis rubra pilaris-like, keratosis pilaris-like, petechial, and ichthyosiform eruptions. Photosensitive rashes occurred on ponatinib and bosutinib, while pustular eruptions, plaques, and eczematous eruptions occurred on bosutinib and ascimnib. cAEs were treated with topical steroids (cAEs=14), emollients (cAEs=10), and antihistamines (cAEs=9); TKI dose was held or discontinued for 17 events. The median duration of cAE ranged from 35 days with asciminib to 91.5 days with bosutinib. 60.5% of events presented within 90 days of medication initiation. No patients required hospitalization for the cAEs; the majority were grade 1 severity (57.2%). There was a significant association between female sex and cAE development (OR 3.30, p=0.003), but no association for age, race, ethnicity, prior CML treatments, and initial dosage. We present a detailed characterization of real-world presentations of cAEs developing on ponatinib, bosutinib, and asciminib, with observed incidence rates of 16.3%, 8.8%, and 6.3%, respectively. The significantly increased risk in females aligns with prior literature, possibly due to differences in body type, medication adherence, or reporting. Our limitations include retrospective design and single institution use.