MRD Monitoring Useful Across Risk Groups in ALL

The use of minimal residual disease (MRD) monitoring has been established as a valuable tool in various cancers, notably acute lymphoblastic leukemia (ALL). Among its uses in ALL is patient stratification, from low-risk to very-high-risk groups of patients, offering guidance for clinical decision making.

In a recent paper published in Expert Review of Hematology, researchers outlined the utility of MRD among these patients and how its monitoring at specific timepoints has proven useful for stratifying patients and helping to ensure appropriate treatment decisions.

“MRD monitoring has changed the definition of remission in pediatric ALL,” emphasized the researchers. “Several studies have found a clear correlation between MRD levels and outcome in children with ALL, endorsing the concept that quantification of MRD after induction of chemotherapy provides a reliable measurement of the in vivo drug sensitivity of leukemic blasts, and therefore guide patients’ stratification and risk-based therapeutic approaches in the context of well-designed clinical studies.”

Among patients with low-risk disease, who have favorable 5-year survival rates, MRD has proven useful in determining patients with highly curable disease, which can help avoid short-term morbidity and mortality as well as long-term sequelae. Recently, long-term study results showed high survival rates among patients with B-cell precursor ALL (BCP-ALL) who were included in the trial after having rapid and significant disease clearance. Among these patients, the estimated 5-year event-free survival rate was 92% and estimated 5-year overall survival rate was 96%.

Among patients with high-risk ALL subtypes, intensive chemotherapy is continued for children and adolescents after achieving multiparametric flow cytometry or immunoglobulin/T-cell MRD negativity following remission induction. In one ongoing study, patients are stratified into the high-risk group if their MRD is ≥5x10-4 following consolidation treatment or if they have BCP-ALL and have polymerase chain reaction (PCR)-determined MRD ≥5x10-4 after induction treatment and are still MRD positive following consolidation treatment.

MRD is also used among patients with very-high-risk disease that is associated with a poor prognosis despite receiving aggressive chemotherapy. For these patients, who are MRD positive following induction and continue to be MRD positive following consolidation treatment, MRD is used prior to transplantation to determine risk of relapse following the procedure.

As MRD continues to have an integral role in patient stratification in ALL, novel methods are entering the arena, offering potential for more specific and sensitive monitoring that can in turn lead to optimized stratification and targeted intervention.

“The new tools of digital droplet PCR, next-generation sequencing, and next-generation flow cytometry, the standardization of which is currently ongoing has shown to be important to evaluate MRD in the research setting, and are partially already incorporated and will be soon more and more incorporated in clinical trials due to their ability to overcome the limitation of standard approaches,” explained the researchers.

However, they add that these methods are time consuming and costly due to a need for individual design and validation for each mutation. As a result, say the researchers, these methods may be appropriate for MRD monitoring of commonly occurring variants but may be more challenging for less common variants that require a personal assay design.

Reference

Ceppi F, Rizzati F, Colombini A, Conter V, Cazzaniga G. Utilising the prognostic impact of minimal residual disease in treatment decisions for pediatric acute lymphoblastic leukemia. Expert Rev Hematol. 2021;14(9):795-807. doi:10.1080/17474086.2021.1967137