Novel therapeutic approaches for acute lymphoblastic leukemia

Therapy for ALL in adults remains a tremendous challenge for clinicians. The use of pediatric-intensive regimens in young and middle-aged adults shows promise in improving outcomes. The addition of monoclonal antibody therapy to chemotherapy appears to hold great promise in lessening relapse rates. The anti-CD20 antibody, rituximab, which has been of such benefit in patients with non-Hodgkin lymphoma, now seems poised to bring significant benefit to adults with ALL. Other monoclonal antibody approaches are in earlier stages of development, but will likely be of significant benefit. The BiTE antibody, blinatumomab, represents an exciting new approach in this arena. As new molecular abnormalities are identified in ALL, these will certainly become new targets for drug development. The increasing use of MRD testing by molecular or flow cytometric techniques will also be invaluable in further refining prognostication in ALL in helping with the selection of patients most likely to benefit from BMT. Several new small molecules and chemotherapeutic agents will, it is hoped, also find a niche in the therapy for ALL. Early examples including NOTCH1 inhibitors; hypomethylating agents such as decitabine, folic acid, antagonists, flavopiridol, bortezomib, and mTOR inhibitors will all hopefully find a role in the therapy for this challenging disorder. Although many challenges remain, there is hope that the therapy for adults with ALL can make significant progress in the next few years, in comparison with the relative plateau that has been experienced over the last several decades.