Disparities in Frontline Treatment and Overall Survival in the Era of Targeted Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia: 2004-2021

Background

The treatment of chronic myeloid leukemia (CML) was revolutionized in 2001 with the BCR::ABL tyrosine kinase inhibitor (TKI), imatinib; with multiple TKIs introduced in subsequent years. In this study we examine how survival has improved in CML patients with the availability of new TKI’s and identify disadvantaged minority groups with disparate overall survival (OS).

Methods

The National Cancer Database was used to identify CML patients. Demographic, treatment, and OS were compared by year of diagnosis and TKI availability: 2004-2005 imatinib, 2006-2011 dasatinib and nilotinib, 2012-2020 bosutinib & ponatinib, and 2021 asciminib.

Results

Of 44,993 CML patients, 55.8% were male and 82.5% were White, with median age of 58-years. Untreated patients (due to contraindication or early death) decreased by each time period, from 17.8% in the imatinib era to 7.8% in 2021. The rate of transplant decreased from 2.5% from 2004-2005, to 0.8% in 2021. For 2004-2005 median OS was 11.5 years (95%CI 10.6-12.5). This increased to 13.6 years (95%CI 13.1-14.1) for 2006-2011, with median OS unreached for 2012-2020. Survival at 1-, 5-& 10-years was improved for each subsequent period, with 5-year OS 65%, 71%, & 76%, respectively, p<0.001. On multivariate cox-regression adjusted for year of diagnoses, features associated with reduced OS included age (HR 1.06 [95%CI 1.05-1.06], p<0.001), Black race (HR 1.11 [95%CI 1.05-1.18], p<0.001), increased comorbidity index (HR 1.94 [95%CI 1.84-2.04], p<0.001), uninsured (HR 2.20 [95%CI 2.01-2.41], p<0.001), or insured through Medicaid (HR 2.40 [95%CI 2.23-2.58], p<0.001).

Conclusions

Survival for CML patients has significantly improved during the last 20-years with the availability of additional TKIs, likely related to increased options for patients with resistance or intolerance. However, patients from traditionally underserved populations, including patients who are underinsured or from racial minority groups, continue to have reduced OS. Efforts to improve access to care for underserved populations is vital.