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. Cancer 2012. © 2012 American Cancer Society.