A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma

BACKGROUND: High-dose chemotherapy combined with autologous stem-cell transplantation (ASCT) is the standard therapy for refractory/relapsed aggressive lymphoma. In the era of rituximab-containing frontline regimens, it is becoming more challenging to salvage patients in this setting, and novel approaches are required. This is a randomized study evaluating the safety and efficacy of standard-dose ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy (Z-BEAM) and ASCT in refractory/relapsed aggressive lymphoma. METHODS: Forty-Three patients with CD20⁺-aggressive lymphoma were randomized to a treatment arm (Z-BEAM, n = 22) or control arm (BEAM alone, n = 21). Ibritumomab tiuxetan was given at 0.4 mCi/kg on day -14 before ASCT. RESULTS: Patient characteristics, engraftment kinetics, and toxicity profile were similar between the 2 groups. Two-year progression-free survival (PFS) for all patients was 48% (95% confidence interval, 32%-64%): 59% and 37% after Z-BEAM and BEAM alone, respectively (P =.2). Multivariate analysis identified advanced age (hazard ratio [HR], 8.3; P =.001), high-risk disease (relapse within 12 months of diagnosis and/or secondary International Prognostic Index >2; HR, 2.8; P =.04), positive positron emission tomography-computed tomography pretransplant (HR, 2.4; P =.07), and BEAM alone (HR, 2.8; P =.03) as poor prognostic factors. Intermediate-risk patients with 1 or 2 risk factors had better PFS with Z-BEAM compared with BEAM: 69% and 29%, respectively (P =.07). Two-year overall survival was 91% and 62% after Z-BEAM and BEAM, respectively (P =.05). Similar prognostic factors determined survival. The HR for BEAM alone in the multivariate analysis was 8.1 (P =.01). CONCLUSIONS: Standard-dose ibritumomab tiuxetan combined with BEAM high-dose chemotherapy is safe and possibly more effective than BEAM alone as a conditioning regimen for ASCT in the era of rituximab-containing chemotherapy regimens.