title: Phase I study of a modified regimen of ⁹⁰Yttrium-ibritumomab tiuxetan for relapsed or refractory follicular or transformed CD20+ non-Hodgkin lymphoma.
abstract: Radioimmunotherapy capitalizes on the radiosensitivity of non-Hodgkin lymphoma (NHL) and the targeted nature of monoclonal antibodies. In an attempt to reverse bone marrow infiltration with B-cells and optimize the biodistribution of Yttrium-90 (⁹⁰Y)-ibritumomab tiuxetan, we conducted a phase I study combining a single course of ⁹⁰Y-ibritumomab tiuxetan after a 4-weekly course of rituximab in relapsed or refractory low-grade or transformed CD20+ B-cell NHLs with <25% marrow involvement. The 0.4 mCi/kg dose was associated with 80% grade-4 cytopenias. Dose escalation was held, and 6 patients were enrolled at a 0.3 mCi/kg cohort. As the 0.3 mCi/kg dose was well tolerated, the 0.4 mCi/kg cohort was expanded to 6 additional patients. In the expansion cohort, grade-4 cytopenia developed in 33%. Further dose escalation was held, and the maximum tolerated dose was determined at 0.4 mCi/kg. With this regimen, marrow involvement decreased in all patients with complete clearance in 50%. The overall response rate was 82%. With a median follow-up of 31.7 months, the median progression-free survival and time to next treatment were 12.3 and 10.9 months, respectively. Although this regimen was associated with a high response rate, the hematologic toxicity was higher than with the standard ⁹⁰Y-ibritumomab tiuxetan regimen.
authors.affiliation: Department of Hematology and Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Vaklavas
authors.forename: Ruby F
authors.initials: RF
authors.lastname: Meredith
authors.forename: Sui
authors.initials: S
authors.lastname: Shen
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
authors.forename: Ivana N
authors.initials: IN
authors.lastname: Micallef
authors.forename: Jatin J
authors.initials: JJ
authors.lastname: Shah
authors.forename: Albert F
authors.initials: AF
authors.lastname: LoBuglio
authors.forename: Andres
authors.initials: A
authors.lastname: Forero-Torres
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D016499:Radioimmunotherapy; D016879:Salvage Therapy; D015996:Survival Rate; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan