SOHO State of the Art Updates and Next Questions | Next Questions: Acute Lymphoblastic Leukemia

The integration of immune and targeted therapies into the treatment of acute lymphoblastic leukemia (ALL) has significantly improved outcomes, reduced the intensity and duration of chemotherapy, and the reliance on allogeneic stem cell transplantation (SCT). In younger patients with Philadelphia chromosome (Ph)-negative ALL, treatment with Hyper-CVAD and blinatumomab +/- inotuzumab has improved the 3-year overall survival (OS) to above 85%. In older patients, using less intensive chemotherapy (mini-Hyper-CVD) in combination with inotuzumab and blinatumomab has improved the 5-year OS rate to 50%. In Ph⁺ ALL, the chemotherapy-free combinations of blinatumomab and ponatinib (or dasatinib) have become a new standard of care resulting in 3-year OS of 85% to 90%. Because the methotrexate-cytarabine courses were omitted in the nonchemotherapy regimens, central nervous system (CNS) relapses were noted, particularly in patients with a WBC count > 70 × 10⁹/L, requiring to consider increasing the number of prophylactic intrathecals (from 12 to 15) and perhaps developing a CNS risk-directed high-dose systemic chemotherapy. In relapsed/refractory ALL, a dose-dense regimen integrating blinatumomab and inotuzumab with low-intensity chemotherapy followed by consolidation with chimeric antigen receptor T-cell therapy is being investigated. The detection of measurable residual disease (MRD) following ALL therapy is predictive of disease relapse. Using next-generation sequencing allows the detection of MRD at 1 × 10⁻⁶ which was shown to be superior to multiparameter flow cytometry and polymerase chain reaction in predicting relapse, and could be used to decide on the duration of therapy or need to change therapy. Herein, we review the recent updates and areas of unmet need in ALL.