Real world performance of the CALGB 10403 regimen in young adults in the United States Open Access

• Efficacy and safety of the C10403 regimen for newly diagnosed AYA ALL patients in the real world are comparable to the prospective trial.

• Completing the regimen through maintenance therapy remains a challenge for patients and clinicians in adult oncology clinics.

The CALGB 10403 (C10403) trial prospectively demonstrated the safety and efficacy of administering an asparaginase-containing pediatric regimen for the treatment of adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL). Since its implementation as standard-of-care, it is unknown how the C10403 regimen performs beyond the clinical trial setting. To bridge this knowledge gap, we designed a multi-center retrospective cohort study to examine the safety, efficacy and challenges with completing C10403 in the “real-world.” From October 2012 through June 2020, 139 patients began induction as per the C10403 regimen across six U.S. academic cancer centers. The median age was 26 years (range, 17-39), 69% were male, 55% were non-Hispanic white, and 27% were Hispanic. Among them, 122 (88%) patients achieved CR/CRi with C10403, 48 (35%) completed maintenance therapy, and 47 (34%) changed post-remission regimens while in CR/CRi. The 3-year event-free survival (EFS) was 66% (95% CI: 55%, 74%) and 3-year overall-survival (OS) was 81% (95% CI: 74%, 87%). Four deaths occurred while on C10403 treatment: one during induction and three later in the treatment course. The most common grade 3 or 4 adverse events during induction included ALT elevation (22%) and sepsis (14%). B-cell immunophenotype (HR 2.45, 95% CI: 1.09, 5.48), Ph-like genetics (3.05, 95% CI: 1.25, 7.44), and Hispanic ethnicity (2.00, 95% CI: 1.06, 3.78) were associated with worse EFS in univariate analyses. Overall, these real-world results are comparable to those from the C10403 trial. Further improvements are needed to enhance outcomes and regimen tolerability in the AYA population.