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: Christos Vaklavas, Ruby F Meredith, Sui Shen, Susan J Knox, Ivana N Micallef, Jatin J Shah, Albert F LoBuglio, Andres Forero-Torres
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 28 Issue 5 Pg. 370-9 (Jun 2013) ISSN: 1557-8852 [Electronic] United States
• PMID: 23530878 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD20
• Yttrium Radioisotopes
• ibritumomab tiuxetan

Topics

• Adult
• Aged
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Antigens, CD20 (metabolism)
• Drug Resistance, Neoplasm
• Female
• Humans
• Lymphoma, Non-Hodgkin (immunology, mortality, therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Grading
• Neoplasm Recurrence, Local (immunology, mortality, therapy)
• Neoplasm Staging
• Prognosis
• Radioimmunotherapy
• Salvage Therapy
• Survival Rate
• Tissue Distribution
• Yttrium Radioisotopes