Disparities in frontline treatment and overall survival in the era of targeted tyrosine kinase inhibitor therapy for chronic myeloid leukemia: 2004-2021.
Authors: Victoria Vardell, Srinivas Kiran Tantravahi
Journal: Journal of Clinical Oncology (2024)

11187 Background: The treatment of chronic myeloid leukemia (CML) was revolutionized in 2001 with the introduction of the BCR::ABL tyrosine kinase inhibitor (TKI), imatinib. In 2006, dasatinib was approved, followed by nilotinib in 2007. Two other TKIs, bosutinib &amp; ponatinib were approved in 2012, followed by the allosteric ABL myristoyl inhibitor asciminib in 2021, providing multiple options for patients (pts) who have refractory disease. In this study we examine how survival has improved in CML pts with the availability of multiple TKI’s and identify disadvantaged socioeconomic &amp; demographic groups which continue to have disparate survival. Methods: The National Cancer Database was used to identify CML pts diagnosed (dx) from 2004-2021. Demographic, treatment, &amp; overall survival (OS) were compared by era of TKI availability, with pts dx from 2004-2005 considered to be treated in the imatinib era, 2006-2011 for dasatinib &amp; nilotinib, 2012-2020 with access to bosutinib &amp; ponatinib, and 2021 for asciminib. Results: Of 44,993 CML pts identified, 55.8% were male &amp; 82.5% were White, with median age of 58 years. The portion of pts who were untreated (due to contraindication or early death) decreased by each time period, from 17.8% in the imatinib era to only 7.8% in 2021. The rate of upfront transplant decreased from 2.5% from 2004-2005, to 0.8% in 2021. For dx 2004-2005 median OS was 11.5 yrs (95% CI 10.6-12.5). This increased to 13.6 yrs (CI 13.1-14.1), with age-adjusted hazard ratio (HR) of 0.86 (CI 0.81-0.91) for pts dx 2006-2011, with median OS unreached for 2012-2020, HR 0.67 (CI 0.63-0.71, p&lt;0.001); referenced to 2004-2006. Survival at 1-, 5- &amp; 10-yrs was improved for each subsequent time period of dx, with 5-yr OS of 65%, 71%, &amp; 76%, respectively, p&lt;0.001. On multivariate cox regression adjusted for yr of dx, features associated with reduced OS included age (HR 1.06 [95% CI 1.05-1.06], p&lt;0.001 for each yr), Black race (HR 1.11 [95% CI 1.05-1.18], p&lt;0.001), increased comorbidity index (HR 1.94 [95% CI 1.84-2.04], p&lt;0.001 for index ≥2), uninsured (HR 2.20 [95% CI 2.01-2.41], p&lt;0.001), or insured through Medicaid (HR 2.40 [95% CI 2.23-2.58], p&lt;0.001). Conclusions: Survival for CML pts has significantly improved during the last 20 yrs with the availability of each additional TKI, likely related to increased treatment options for pts with resistance or intolerance. Additional TKI options, particularly approval of ponatinib for patients with T315I mutation, have a secondary benefit of decreasing the utilization of allogenic transplant. Though survival has improved for all pts, pts from traditionally underserved populations, including pts who are underinsured or from racial minority groups, have reduced OS. Continued advances in treatment &amp; efforts to improve access to care for underserved populations is vital to achieve equitable survival outcomes in CML.