Inflammatory/Immune Adverse Events in Chronic Myeloid Leukemia Patients during Treatment with Bosutinib

• Published in: Blood 2024-11, Vol.144, p.6595-6595
• Main Authors: Agostani, Elena, Tassistro, Elena, Antolini, Laura, Gambacorti-Passerini, Carlo
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-206023

Introduction Bosutinib, a third-generation tyrosine kinase inhibitor (TKI), is effective in treating Chronic Myeloid Leukemia (CML) patients who are resistant or intolerant to previous TKIs. Unlike other TKIs, bosutinib lacks inhibition of c-KIT and PDGFR, potentially contributing to its unique tolerability profile. It targets Bcr/Abl and SRC kinases, particularly Lyn, which plays a crucial role in immune response, particularly in myeloid cells and B lymphocytes, where it is involved in signaling cascades essential for self-tolerance and anergy. The susceptibility of Lyn -/- mice to lupus-like autoimmune disorders and the deregulation of Lyn- dependent pathways in patient with lupus were previously shown. The study aims to assess the time-adjusted rate (TAR) of inflammatory/immune-related adverse events (irAEs) in bosutinib-treated patients. Methods This retro-prospective observational cohort study was conducted involving 60 CML patients treated with bosutinib at San Gerardo Hospital from 2006 to 2020, with a minimum follow-up of three months, as part of bosutinib registration trials. The study also included 10 imatinib-treated patients enrolled as a control group in the same clinical studies. Data on adverse events (AEs) were collected and classified according to CTCAE terminology (v5.0). Patient characteristics were described using median and interquartile ranges for continuous variables and frequencies and percentages for categorical variables. The distribution of irAEs was displayed using a bar plot. The TAR of first and repeated AEs was calculated along with 95% confidence intervals (CI) using an exponential model. The cumulative incidence probability of the first AE was estimated using the Kaplan-Meier method. Analyses were performed with Stata 15 software. Results Of the 60 bosutinib-treated patients, 34 (56.6%) were male and almost all the patients were caucasian (98.3%) with a median age of 62.8 years. The median follow-up duration was 47.9 months (IQR 38.4-121.8 months). Median bosutinib dose was 489.2 mg/day (IQR 437.1- 509.6 mg/day). IrAEs occurred in 55% of the subjects (n=33) with many experiencing multiple or recurrent events. A total of 94 irAEs were reported (2.3% of total AEs, n=4060), including giant cell arteritis, psoriasis, erythema nodosum, articular pain, pleural effusion and three cases of recurrent sterile pneumonia. Most irAEs occurred in the respiratory system (52.1%, n=49), followed by those in the musculoskeletal system and co