Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma

Objective: To determine the safety and outcome following standard-dose ibritumomab tiuxetan followed by BEAM high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with chemo-refractory aggressive non-Hodgkin's lymphoma. Patients and Methods: The study included 23 patients, median age 55 years (range, 35-66) with chemo-refractory lymphoma, either primary refractory (n = 11) or in refractory relapse (n = 12). Rituximab 250 mg/m² followed by ibritumomab tiuxetan 0.4 mCi/kg were given on day -14 and high-dose BEAM chemotherapy started on day -6. Results: All patients engrafted. Twenty-one patients are evaluable for response; 11 achieved CR, 9 achieved PR, 5 of whom converted to CR with additional radiation therapy (overall CR rate 76%). With a median follow-up of 17 months (range, 4-27) 16 patients are alive and 12 are progression-free. The estimated 2-year overall and progression-free survival are 67% (95% CI, 46-87%) and 52% (95% CI, 31-72%), respectively. The day-100 rate of treatment-related mortality was 9% (95% CI, 2-33%) and the 2-year cumulative incidence of relapse was 31% (95% CI, 17-57%). Extensive prior therapy (>3 lines), high LDH and IPI score at ASCT, bulky disease, and progression during last chemotherapy were risk factors for reduced survival. Conclusion: Ibritumomab tiuxetan-BEAM and ASCT is relatively safe and may improve outcome in patients with refractory lymphoma. Although excess nonrelapse mortality can not be ruled out, relapse rate was relatively low, resulting in improved outcome. Standard-risk patients with chemo-sensitive disease may also benefit from ibritumomab tiuxetan-BEAM and ASCT. This hypothesis merits further study in larger-scale prospective randomized studies.