title: Monoclonal antibody-based therapies in the treatment of acute lymphoblastic leukemia.
abstract: Recent studies have suggested that pediatric-intensive chemotherapy regimens can improve outcomes in adults with acute lymphoblastic leukemia (ALL) up to the age of 45. Above this age, toxicities increase. Monoclonal antibody-based therapies bring the promise of increased response rates without excessive toxicity. The addition of rituximab to combination chemotherapy has shown encouraging results. Newer monoclonal antibody-based therapies linked to cytotoxic agents show promise. These include inotuzumab ozogamicin, an anti-CD22 antibody linked to calicheamicin that has produced significant single-agent responses in relapsed and refractory ALL. Other monoclonal antibodies linked to plant or bacterial toxins are in earlier stages of development. Blinatumomab is a novel bispecific T-cell engaging antibody that combines single chain antibodies to CD19 and CD3 and brings a T cell in close proximity to a leukemic lymphoblast with resulting redirected lysis. This agent has demonstrated encouraging results in both the minimal residual disease setting and the relapsed/refractory setting. Autologous chimeric antigen receptor cells have shown promising responses in indolent B-cell lymphoid malignancies and are being tested in ALL. Many of these agents have the potential to increase response rates in older adults. Trials of many of these monoclonal antibody-based therapies are in various stages of development in the treatment of newly diagnosed ALL.
authors.affiliation: From the Division of Hematology, Mayo Clinic, Rochester, MN.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
mesh_terms: D018033:Antibodies, Bispecific / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000737:chemistry; D000080045:Inotuzumab Ozogamicin; D058990:Molecular Targeted Therapy / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D000069283:Rituximab / Q000008:administration & dosage; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C497867:CD22 protein, human; D000922:Immunotoxins; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab; D000069283:Rituximab; C510808:blinatumomab; D000080045:Inotuzumab Ozogamicin