Adverse Events and Treatment Adjustments Among Newly Diagnosed Patients with Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors: A Comprehensive Data Analysis of Medicare Fee-for-Service and Commercial Plans in the United States

Introduction: Despite the established benefits of first-generation (1G) and second- generation (2G) tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML), patients often discontinue treatment due to adverse events (AEs). The real-world rates of AEs and treatment adjustments with 1G and 2G TKIs in patients with CML are not well documented. This real-world study assessed the rate of AEs and treatment adjustments with 1G and 2G TKIs in CML, using data from two large claims databases representing two distinct age groups in the US.

Methods: Patients with CML receiving 1G (imatinib) or 2G (dasatinib, nilotinib, bosutinib) TKIs were identified in the IQVIA PharMetrics® Plus Commercial database (07/2016-03/2023) and Medicare Fee-for-Service (FFS) database (01/2017-06/2022). The proportions of patients with any-grade AEs (identified using ICD-10 diagnosis codes) during the treatment period and treatment adjustments (discontinuation with or without dose reduction, dose reduction, and treatment switch) during the follow-up period were descriptively reported by 1G and 2G TKIs for first line treatment in Medicare patients and summarized for indexed 1G or 2G TKIs in any line in commercial patients.

Results: A total of 2,546 commercial patients (n=882 [1G TKI; 34.6%], n=1,664 [2G TKIs; 65.4%]) were included. Among 2G TKIs, dasatinib was the most common (68.8%), followed by nilotinib (22.7%) and bosutinib (8.5%). Among the 1G/2G TKI groups, the median ages were 55.0 (range: 18.0-86.0) and 52.0 (18.0-85.0) years, respectively, with 43.3% and 44.1% being female. During the baseline period, 17.9%/18.0% of 1G/2G TKI groups were classified to have severe Darkow disease complexity. The mean [standard deviation (SD)] time on treatment with 1G/2G TKIs was 20.6 (19.2)/21.6 (18.3) months. Common AEs during treatment included fatigue (26.5%/30.5% for 1G/2G TKIs, respectively), nausea/vomiting (17.5%/17.8%), peripheral edema (17.0%/12.1%), diarrhea (16.4%/12.6%), cardiac arrhythmias (15.1%/19.2%), headache (11.6%/16.5%), arterial occlusive event (13.2%/11.2%), rash (7.8%/12.7%), thrombocytopenia (7.7%/16.7%) and pleural effusion (6.9%/12.3%). The mean (SD) follow-up period for 1G/2G TKIs was 31.8 (20.8)/29.3(19.2) months. During the follow-up period, 47.1%/37.4% of patients using 1G/2G TKIs, respectively, discontinued treatment, 16.3%/25.6% had dose reduction, and 34.1%/28.2% switched treatment.

A total of 1,846 Medicare patients (n=1,108 [1G TKI; 60.0%] and n=738 [2G TKI; 40.0%], respectively) were included. Among 2G TKIs, dasatinib was the most common (74.5% Medicare), followed by nilotinib (18.8%) and bosutinib (6.6%). Among the 1G/2G TKI groups, the median ages were 75.0 (range: 36.0-97.0) and 73.0 (42.0-96.0) years, respectively, with 46.8% and 44.4% being female. During the baseline period, 29.7%/32.5% of 1G/2G TKI groups were classified to have severe Darkow disease complexity. The mean (SD) time on treatment with 1G/2G TKIs was 18.5 (16.9)/14.4(14.9) months. Common AEs included fatigue (41.1%/34.8%), peripheral edema (41.0%/26.2%), nausea/vomiting (26.8%/20.5%), diarrhea (26.8%/18.4%), renal insufficiency (21.6%/17.8%), thrombocytopenia (20.5%/22.4%), pleural effusion (18.7%/34.6%), constipation (16.3%/18.7%), rash (15.3%/13.8%) and peripheral arterial occlusive disease (14.3%/11.7%). The mean (SD) follow-up period for 1G/2G TKIs was 31.1(17.9)/32.2(18.0) months. During the follow-up period, 56.4%/70.3% using 1G/2G TKIs, respectively, discontinued treatment, 28.6%/29.7% had dose reduction, and 22.9%/35.1% switched treatment.

Conclusions: This real-world study has shown that AEs are common in both 1G and 2G TKIs among commercial and Medicare patients with CML. Higher proportions of AEs were observed in Medicare patients who were on average 20 years older than commercial patients. Most patients with CML underwent some form of treatment adjustments while on either 1G or 2G TKIs, with approximately half of both cohorts discontinuing 1G TKI and over one-third of commercial and nearly three-quarters of Medicare patients discontinuing 2G TKIs. The significant burden of AEs and high discontinuation rates highlight unmet needs in the management of CML.