Overcoming barriers to clinical trial enrollment among adolescents and young adults with acute myeloid leukemia: Insights from a large academic cancer center

Abstract Background: Adolescents and young adults (AYAs, age 15-39 years) with acute myeloid leukemia (AML) experience disparities in outcomes, partly driven by socioeconomic factors and limited participation in cancer clinical trials. Our group previously reported that receipt of induction therapy in a clinical trial was associated with improved overall survival among AYAs with AML (Hill et al. JCO 2025). Here, we describe overall clinical trial participation rates in this population and characterize the barriers that prevented trial enrollment among AYAs with AML treated at a large cancer center with a robust AML trial portfolio. Methods: We retrospectively reviewed all AYAs with AML treated at MD Anderson Cancer Center between March 2013-2023. Patient sociodemographic and clinic data were abstracted from the electronic medical record. The reasons for non-enrollment on a clinical trial were captured from research study and treating physician notes and categorized as follows: 1) disease-related (e.g., myeloid sarcoma, progressive disease needing urgent treatment initiation, lack of lower-intensity clinical trial options due to TP53-mutated disease); 2) insurance or financial barriers (lack of insurance, insurance denial, patient's financial constraints); 3) ineligibility due to patient factors (e.g., comorbidities, organ impairment, concomitant malignancy or prior chemotherapy); 4) patient or treating physician preference; and 5) unknown. Results: Among 190 AYAs with AML (median age 31 years, range 17-39 years, 43% had adverse risk by ELN 2022), 135 (71%) were enrolled in a clinical trial. There was no difference in the rates of clinical trial enrollment among patients from low versus high Area Deprivation Index (ADI) national (67 and 68 patients) or state (69 and 66 patients) ranks. Of the 55 patients (29%) treated outside of a clinical trial, the most common barriers were – insurance/ financial constraint (33%), ineligibility due to patient factors (22%), disease-related factors (18%), unknown reasons (16%), and patient/treating physician choice (11%). Treatment on a clinical trial was independently associated with a significantly lower hazard of death compared to patients treated outside of clinical trial (HR-0.46, 95% CI 0.29-0.72, p=0.001) in a multivariate analysis. Conclusion: In a large academic cancer center with a robust portfolio of AML clinical trials available, most AYAs with AML participated in a trial, demonstrating the feasibility of enrolling this historically underrepresented population. However, insurance/financial barriers and patient eligibility factors remain substantial barriers to enrollment. Expanding eligibility criteria and enhancing patient financial support and navigation may further improve AYA' access to and participation in cancer clinical trials.