title: Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma.
abstract: The clinical development and US Food and Drug Administration approval in 1997 of the monoclonal anti-CD20 antibody rituximab have been major treatment advances for patients with B-cell non-Hodgkin's lymphoma (NHL). Rituximab produces responses in approximately 50% of cases of relapsed, low grade NHL. Most of these responses are partial remissions; cure remains elusive. One way to enhance the effectiveness of monoclonal antibodies is to chelate radionuclides such as yttrium-90 ((90)Y) to the antibody. ( 90)Y is a high-energy, beta-emitting radioisotope that delivers most of its radiation over a path length of 2 to 5 mm. Therefore, the antibody delivers, or targets, the radiation only to CD20+ cells, sparing normal cells from the radiation. Ibritumomab is the murine anti-CD20 antibody that was engineered to develop the human chimeric antibody rituximab. Tiuxetan is a linker/chelator that is attached to the antibody to form ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA). Zevalin can be reacted with (111)indium ((111)In) for imaging and (90)Y for therapy. Phase I studies of Zevalin have determined that patients with a baseline platelet count greater than 150,000 10(6)/L receive 0.4 mCi/kg. Patients with a platelet count of 100 to 149,000 10(6)/L should receive 0.3 mCi/kg. Zevalin has a higher overall response rate (ORR) than its cold antibody counterpart rituximab, as demonstrated in two separate clinical trials. The first trial (IDEC 106-04) randomized 143 rituximab-naïve patients with relapsed NHL to receive rituximab or Zevalin. The ORR for Zevalin was 80% compared with 56% for rituximab (P = 0.002). The second trial (IDEC 106-06) tested the efficacy of Zevalin in patients who were rituxan-refractory; the ORR was 74%. The main toxicity of Zevalin was reversible myelosuppression. These studies indicate that radiolabeled anti-CD20 antibodies can produce a higher ORR than rituximab. Single-dose Zevalin is another treatment alternative for patients with relapsed low grade NHL. It is well-tolerated even by older adults. The exact role of Zevalin in the therapy of NHL is undetermined. New studies are underway to explore whether patients can safely receive a second dose of Zevalin and to combine Zevalin with high-dose chemotherapy and stem cell rescue. The outcome of these studies will be helpful in deciding how best to integrate this new modality into the treatment paradigm of NHL.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic and Mayo Foundation, 200 First Street, Rochester, MN 55905, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Alcindor
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan