Evaluation and management of measurable residual disease in acute lymphoblastic leukemia

Abstract

With standard chemotherapy regimens for adults with acute lymphoblastic leukemia, approximately 90% of patients achieve complete remission. However, up to half of patients have persistent minimal/measurable residual disease (MRD) not recognized by routine microscopy, which constitutes the leading determinant of relapse. Many studies in pediatric and adult populations have demonstrated that achievement of MRD negativity after induction chemotherapy or during consolidation is associated with significantly better long-term outcomes, and MRD status constitutes an independently prognostic marker, often superseding other conventional risk factors. Persistence of MRD after intensive chemotherapy is indicative of treatment refractoriness and warrants alternative therapeutic approaches including allogeneic stem cell transplantation, blinatumomab, or investigational therapies such as inotuzumab ozogamicin or chimeric antigen receptor T cells. Furthermore, the incorporation of novel monoclonal antibodies or potent BCR-ABL1 tyrosine kinase inhibitors, such as ponatinib into frontline treatment may have the advantage of achieving higher rates of MRD negativity while minimizing chemotherapy-related toxicities. Many studies are therefore ongoing to determine whether this strategy can improve cure rates without the need for allogeneic stem cell transplantation.