title: Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy.
  
  
  METHODS
  Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20(+) B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass > or = 5 cm.
  
  
  RESULTS
  The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/microL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (> or = 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody).
  
  
  CONCLUSIONS
  These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.
authors.affiliation: Divisions of Hematology and Nuclear Medicine, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Witzig
authors.forename: C A
authors.initials: CA
authors.lastname: White
authors.forename: G A
authors.initials: GA
authors.lastname: Wiseman
authors.forename: L I
authors.initials: LI
authors.lastname: Gordon
authors.forename: C
authors.initials: C
authors.lastname: Emmanouilides
authors.forename: A
authors.initials: A
authors.lastname: Raubitschek
authors.forename: N
authors.initials: N
authors.lastname: Janakiraman
authors.forename: J
authors.initials: J
authors.lastname: Gutheil
authors.forename: R J
authors.initials: RJ
authors.lastname: Schilder
authors.forename: S
authors.initials: S
authors.lastname: Spies
authors.forename: D H
authors.initials: DH
authors.lastname: Silverman
authors.forename: E
authors.initials: E
authors.lastname: Parker
authors.forename: A J
authors.initials: AJ
authors.lastname: Grillo-López
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000473:pathology; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D012008:Recurrence; D000069283:Rituximab; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes; D000069283:Rituximab