Philadelphia chromosome-positive (Ph⁺) B-cell acute lymphoblastic leukemia (B-ALL) and Ph-like ABL-class B-ALL account for nearly 10% of all pediatric ALL cases and are historically associated with inferior outcomes. These subtypes share similar gene expression and clinical profiles, poor response to traditional chemotherapy, and sensitivity to ABL-targeted tyrosine kinase inhibitors (TKIs) such as imatinib or dasatinib.

For Ph⁺ B-ALL, early and continuous TKI administration in combination with an intensive chemotherapy backbone has significantly improved response rates and event-free survival (EFS), as well as eliminated the need for hematopoietic stem cell transplant in first remission for most children. This molecularly-targeted approach has revolutionized the treatment paradigm for these patients with five-year EFS and overall survival averaging 60% and 80%, respectively. Moreover, based on reports from small patient cohorts, a similar treatment strategy has also resulted in favourable outcomes for patients with ABL-class Ph-like B-ALL, although a standard of care treatment regimen remains to be established for these patients. Nevertheless, over the last two decades, despite improved outcomes in the TKI era, children with Ph⁺ ALL continue to suffer from higher rates of relapse, significant treatment-related toxicities and increased long-term side effects compared to Ph^– ALL patients. Therefore, there remains a need for further treatment optimization.

The Children’s Oncology Group (COG) AALL2131 trial is an international pilot study that will investigate the benefit of combining standard chemotherapy with TKI and blinatumomab on 3-year EFS for newly diagnosed patients with Ph⁺ or ABL-class Ph-like B-ALL. Post-induction, all patients will receive continuous TKI with a modified chemotherapy backbone that incorporates three cycles of blinatumomab. However, this trial uses clonoSEQ, a next-generation sequencing (NGS) assay by Adaptive Biotechnologies, to detect and monitor minimal residual disease (MRD) for treatment allocation. clonoSEQ is a FDA-cleared MRD assay that offers greater sensitivity (10^-6 vs. 10^-5), a lower rate of indeterminant results (≤5% vs. 15%) and the ability to capture clonal evolution over time – all while being less labor-intensive and having a faster turn-around time – when compared to the conventional assay used to detect and monitor MRD in ALL patients (the Ig/TCR PCR MRD assay). While clonoSEQ is routinely reimbursed by insurance providers in the United States, it is not currently covered in Canada.

Through ACCESS support, eligible patients in Canada will be able to access clonoSEQ NGS MRD testing and, therefore, participate in this high-impact clinical trial that paves a new way in the treatment of patients with Ph⁺ or Ph-like ABL-class B-ALL. The C17 Council will serve as the trial’s Canadian regulatory sponsor and will open the trial at all 16 pediatric oncology centers in Canada.

ACCESS has also supported the conduct of an embedded correlative study, to be led by Dr. Thai Hoa Tran at CHU-Sainte Justine, that will evaluate correlation between TKI levels and outcomes. Therefore, in addition to ACCESS enabling patients in Canada to participate in the AALL2131 trial by providing access to sophisticated, state-of-the-art testing, ACCESS’ support of this trial in Canada is also enabling Canadian investigators to:

1. establish and hold leadership positions in international pediatric oncology consortia;
2. collaborate with these existing consortia to conduct further innovative clinical and translational research.

For more information, please contact Tricia Schneider.