Highly Effective Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia Helps Overcome Social Determinants of Health in Medically Underserved Populations
Authors: Rockwell Bradley , Dhanaraj Nitya , Forsberg Mark , Goel Swati , Levitz David , Gupta Ridhi , Shapiro Lauren , Kornblum Noah , Feldman Eric J. 
Published: December 2024

Introduction: Overall survival (OS) has improved significantly for patients with chronic myeloid leukemia (CML) since the development of BCR/ABL tyrosine kinase inhibitors (TKI). Health care disparities resulting from social determinants of health are key factors in clinical outcomes for patients with cancer. In medically underserved populations, reduced access to primary care results in delays in diagnoses and unmanaged co-morbidities. In addition, lack of medical insurance and financial distress has been shown to be associated with worse outcomes as well as high rates of non-adherence to therapy, a critical factor in the success of TKIs in CML.

Located in the Bronx, New York, the Montefiore-Einstein Comprehensive Cancer Center (MECCC) serves the poorest congressional district in the United States with a high prevalence of patients with low socioeconomic status (SES). As part of an ongoing outcomes-based analysis of patients with hematologic malignancies at MECCC, we evaluated patient demographics, initial TKI choice, and clinical results including achievement of National Comprehensive Cancer Network (NCCN) management guidelines for CML and OS in this vulnerable and medically underserved population.

Methods: We conducted a retrospective analysis on all patients seen at MECCC for the initiation of treatment for CML in chronic phase. Data obtained by searching the electronic medical record system for the diagnosis code of CML.

Results: From 2004-2024, data was available for 104 patients with CML in chronic phase. Sixty-two (60%) were male and 42 (40%) were female with a median age of 53 years (range 15-89). Race/Ethnicity data showed 73% with a minority background, including Hispanic (41%) and non-Hispanic Black (28%). Of the 74 patients with documentation of clinical presentation, 33 (44%) were symptomatic. Seventy-two (69%) patients were treated with imatinib as their initial TKI. Twenty-six (25%) and 6 (6%) received dasatinib and nilotinib, respectively. Three month molecular real-time polymerase chain reaction milestone data using International Scale (IS) was available for 62 patients: 29 (47%) had an IS&gt;10%, 15 (24%) had 1-log reduction (IS 1-10%), 9 (15%) had 2-log reduction (IS 0.1-1%), 6 (10%) had 3-log reduction (0.01-0.1%), 0 had 4-log reduction (0.0032-0.01%), and 3 (5%) had 4.5-log reduction (&lt;0.00325%). Six-month data was available for 62 patients: 16 (26%) had IS&gt;10%, 19 (31%) had 1-log reduction, 14 (23%) had 2-log reduction, 9 (15%) had 3-log reduction, 0 had 4-log reduction, and 3 (5%) had 4.5-log reduction. Twelve-month molecular data for 61 patients showed 9 (15%) had an IS&gt;10%, 12 (20%) had 1-log reduction, 15 (25%) had 2-log reduction, 11 (18%) had 3-log reduction, 3 (5%) had 4-log reduction, and 11 (18%) had 4.5-log reduction. Overall at 6-months, 45 patients (74%) met the NCCN criteria for TKI-sensitive disease with at least a 1-log reduction. At the 12-months, 25 patients (41%) had at least a 3-log reduction, or a major molecular response (MMR), again meeting criteria for TKI-sensitive disease. As per current NCCN guidelines, a total of 20 patients (19%) were eligible for treatment free remission (TFR). Of these, 5 discontinued therapy and 15 elected to continue their TKI. Five-year OS was 91.3%. Of the 9 patients who died, only 1 CML-related death was observed.

Conclusions: We present data for a diverse cohort of CML patients located in one of the poorest areas in the United States. A high number of patients were symptomatic at presentation, which may represent the lack of access to primary care in this economically and social marginalized population. Imatinib was the most common TKI prescribed. Less than half of the patients met MMR at 12 months, a milestone that has been shown to predict future loss of response and ability to achieve TFR. This was confirmed by the low number of patients that met criteria for TFR and ultimately the even lower number of patients that successfully attempted TKI discontinuation. Despite all these unfavorable factors, patients showed an OS similar to that of other clinical data reported in non-minority majority populations. These observations suggests that highly effective drugs, such as TKIs in CML, can help overcome the well-known barriers and poor health outcomes of patients in lower SES. Of particular interest is the observation of the overall lack of CML-related mortality despite failure to achieve strict milestones for TKI management.