The Safety And Efficacy Of Standard-Dose Y-90 Ibritumomab Tiuxetan Combined With High-Dose Beam And Autologous Stem-Cell Transplantation In Patients, Including Those Over 60 Years, With Non-Hodgkin'S Lymphoma

Purpose/Objective: Total-body irradiation (TBI) is an effective component of many autologous stem cell transplantation (ASCT) preparative regimens for non-Hodgkin’s lymphoma (NHL) due to the exquisite radiosensitivity of the disease. Patients over the age of 60, however, are often excluded from receiving TBI-containing regimens because of concerns about treatment-related toxicities. Unfortunately, disease progression accounts for the majority of treatment failures observed after ASCT. In order to reduce toxicity while incorporating the benefits of targeted radioimmunotherapy (RIT), we initiated a phase 2 study with standard-dose 90Y ibritumomab tiuxetan and high-dose BEAM followed by ASCT in patients with high-risk NHL. Materials/Methods: Patients ≥18 years were eligible for this study. However, because of a competing study employing high-dose 90Y ibritumomab tiuxetan, older patients were most likely to accrue to 90Y ibritumomab tiuxetan + high-dose BEAM. Twenty-six patients with a median age of 60 years (range, 20–79) at transplantation were enrolled. Patients presented with CD20+ B-cell NHL, including 10 patients with mantle cell lymphoma and 10 patients with diffuse large cell lymphoma. Disease status included induction failure (n = 7), first partial response (n = 4), first or second relapse (n = 7), high-risk first complete response (CR) (n = 5), and second CR (n = 3). Patients had received a median of 2 prior chemotherapy regimens (range, 1–4). Imaging studies, but not dosimetry, were performed prior to delivery of therapeutic RIT. On day −14, patients were treated with a fixed dose of 90Y ibritumomab tiuxetan of 0.4 mCi/kg. The median administered dose of 90Y ibritumomab tiuxetan was 32 mCi (range, 20–40). On day −7, chemotherapy was initiated with carmustine 150 mg/m2 and repeated on day −6. Cytarabine 800 mg/m2 and etoposide 800 mg/m2 were administered daily from day −5 through day −2, followed by melphalan 140 mg/m2 on day −1. On day 0, a median of 4.5 × 106 CD34+ cells/kg was reinfused into patients. Results: The incidence and severity of toxicities associated with the combination of standard dose 90Y ibritumomab tiuxetan and high-dose BEAM were similar to those with high-dose BEAM alone and included grade 3–4 pulmonary toxicity (n = 4, 15%). The median time to WBC (granulocytes >500/mm3) and platelet engraftment (>20,000/mm3) were 11 days (range 9–26) and 12 days (range 8–24), respectively. With a median follow-up of 14 months, the 1-year overall survival and progression-free survival (PFS) are 90% (95% CI 78–100) and 72% (95% CI 53–91), respectively. The relapse rate is 24% (95% CI 5–43). Conclusions: Standard-dose 90Y ibritumomab tiuxetan and high-dose BEAM with ASCT may be safely administered without dosimetry. Based on analyses of both safety and PFS, this preparative regimen is well tolerated and effective in older patients undergoing ASCT for high-risk NHL.