Abstract IA22: Understanding causes of Inferior Survival in Adolescent and Young Adults with Acute Lymphoblastic Leukemia

Abstract

Abstract Outcomes of AYA patients with ALL remain markedly worse when compared with those of their younger counterparts, as evidenced by a dramatic decline in 5-year survival (<15y: 85.8%; 15-19y: 62.2%; 20-39y: 52.8%). The reason(s) of the observed inferior survival are a source for active investigation, and include disease biology, patterns of treatment and adherence to therapy. While the talk will focus primarily on adherence to therapy, I provide a brief overview of the differences in disease biology and treatment strategy between AYA with ALL and their younger counterparts. Disease biology: The prevalence of hyperdiploidy and ETV6-RUNX1 leukemia (both associated with good prognosis) declines with age at onset of ALL. In contrast, the prevalence of t(9;22) Ph chromosome leading to BCR-ABL1 fusion progressively increases with age, as does the prevalence of T-cell ALL, iAMP21, Ph-like ALL, with a high frequency of alterations of the IKZF1 gene; all associated with poor outcome. Treatment patterns: Adolescents with Philadelphia (Ph)–negative ALL have better outcomes when treated according to pediatric strategies. This has led to the use pediatric-inspired or fully pediatric strategies that have improved outcomes in young adults with Ph-negative ALL. Adherence to oral 6MP: Durable first clinical remission (CR) is desirable and requires a prolonged maintenance phase with daily self-administered oral mercaptopurine. Low mercaptopurine systemic exposure increases relapse risk. Patient adherence to mercaptopurine is a primary determinant of mercaptopurine systemic exposure. In a previous study, we measured mercaptopurine adherence electronically in children with ALL entering maintenance in first CR, using the Medication Event Monitoring System (MEMS®) device, and made several observations. (A) Adjusting for prognosticators, adherence rates <90% are associated with 3.9-fold higher relapse risk. (B) Adherence rates are lower in adolescents (85.4%) vs. children (92.6%). (C) A third of the adolescents are non-adherers. (D) The most common reason for missing 6MP is forgetfulness; adherent adolescents emphasize parental vigilance to overcome forgetfulness. These observations informed a randomized controlled trial (RCT) to enhance 6MP adherence. The Intervention Package (IP) consisted of education, daily personalized text-message reminders from the healthcare provider to the patient and caregiver, daily directly-supervised therapy (DST) by the caregiver. Patients were randomized to education alone (Edu) or IP for 16 weeks. Adolescent baseline non-adherers (adherence <90%) had significantly higher (p=0.008) adherence rates on IP (83.4%) vs. Edu (74.6%), especially the high DST responders (IP: 86.5%, vs. Edu: 74.6% p=0.001). Adolescent baseline adherers (adherence ≥90%) showed no difference (p=0.3) in adherence rates between IP (96.2%) and Edu (95.0%); however, adherence rates drifted down over time (p <0.0001). These findings have led to a large trial that builds upon the results of the previous RCT. In summary, the causes of inferior outcome in AYAs are multifactorial, necessitating a multi-pronged approach to mitigate these differences. Citation Format: Smita Bhatia. Understanding causes of Inferior Survival in Adolescent and Young Adults with Acute Lymphoblastic Leukemia [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA22.