Clinical trial results show low-intensity therapy can achieve positive outcomes for certain pediatric leukemia subtypes

Clinical trial results from St. Jude Children’s Research Hospital demonstrate the benefits of using genomics and early treatment response to guide risk classification of children with B-cell acute lymphoblastic leukemia (B-ALL).

Traditionally, the intensity of a patient’s chemotherapy regime is guided by the National Cancer Institute (NCI) risk classification, which is largely determined by clinical characteristics such as age and white blood cell count at presentation. Through the flagship St. Jude Total Therapy clinical trials, investigators have looked at two genetic subtypes of B-ALL (ETV6::RUNX1 and high-hyperdiploid).

Results showed that patients with ETV6::RUNX1 and high-hyperdiploid B-ALL—who, by NCI risk assessment, would have received a high-intensity treatment regimen—could complete a low-intensity regimen and achieve positive outcomes. These findings appear in the journal Blood.

Enhanced criteria for risk assessment

Risk-based chemotherapy is a tailored approach that adjusts the intensity of treatment based on the individual patient’s risk factors, and its implementation has improved cancer care outcomes. However, traditional risk factors by NCI criteria do not provide a complete picture of prognosis. Modern studies, including the recent St. Jude Total Therapy clinical trials, have refined these criteria by incorporating genetic subtypes and early treatment responses into assessments.

Patients with ETV6::RUNX1 and high-hyperdiploid B-ALL make up 25% and 30% of B-ALL cases, respectively. These patients can be classified as low-risk, provided they have no central nervous system or testicular involvement and respond well to induction (initial) chemotherapy. This approach reflects a shift towards a more individualized risk assessment model, accounting for both genetic and clinical factors to better tailor treatment plans.

“In the St. Jude Total Therapy XV study, we began incorporating genetic information and response criteria into our risk assessment. This risk classification system allows us to identify patients who can be treated with lower-intensity therapies while ensuring that those who require more intensive treatment receive it,” said corresponding author Hiroto Inaba, MD, Ph.D., St. Jude Department of Oncology.

“We strive to be mindful of using only the necessary treatments to achieve a cure, aiming to minimize the risk of enduring health issues and side effects from a child’s cancer treatment,” explained first author Katelyn Purvis, MD, St. Jude Department of Oncology.

Reduced-intensity treatments yield positive outcomes

In this study, researchers evaluated patient outcomes from those enrolled on the St. Jude Total Therapy XV and XVIclinical trials. They looked at the correlation between genomics- and early treatment response-guided risk assessment and patient outcomes. By treating 93% of patients with ETV6::RUNX1 and 54% of those with hyperdiploid B-ALL who were traditionally considered high risk with low intensity chemotherapy, the investigators were able to achieve positive outcomes including excellent event-free survival rates.

“We tailored chemotherapy to better match patient needs and successfully identified who could benefit from low-intensity therapy. This strategy highlights our goal of personalizing treatment based on individual patient characteristics for better outcomes,” explained Inaba.

Patients who would have otherwise been treated with high-risk therapy experienced fewer side effects, such as thrombosis and pancreatitis. The findings suggest that by using genome- and early treatment response-guided risk classification, clinicians and researchers can accurately identify patients who are likely to benefit from less intensive treatment.

“We now have tangible evidence that reduced therapy can be beneficial for some patients, which decreases toxicity,” said Purvis. “Our goal for every child who walks through our doors with leukemia is to not only cure them but also to extend their lives by decades with minimal side effects. We’re proud that we can achieve this for most of our leukemia patients, which is truly remarkable.”