Abstract IA22: Understanding causes of Inferior Survival in Adolescent and Young Adults with Acute Lymphoblastic Leukemia
Authors: Bhatia Smita 
Published: December 2020

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 (&lt;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 &lt;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 &lt;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 &lt;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.