Efficacy and Safety of Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan in Autologous and Nonmyeloablative Stem Cell Transplantation (NST) for Relapsed Non-Hodgkin’s Lymphoma (NHL).

Background: Relapse continues to be the primary cause of treatment failure in patients with NHL undergoing stem-cell transplantation (SCT). The anti-CD20 radioimmunoconjugate ⁹⁰Y ibritumomab tiuxetan has been associated with high-response rates and limited toxicity, making it an ideal candidate for use in transplantation.

Methods: ⁹⁰Y ibritumomab tiuxetan was given at the fixed dose of 0.4 mCi/Kg on day −14 for patients who were candidates for autologous SCT. Chemotherapy consisted of standard BEAM (days −7 to −1). Due to unknown toxicity when combined to fludarabine, ⁹⁰Y ibritumomab tiuxetan was instead given in an escalating phase I schedule (0.2, 0.3 and 0.4 mCi/kg) on day −14 in patients who were candidates for NST and who received fludarabine, cyclophosphamide and rituximab as conditioning, as previously published. Dosimetry was performed for the allo- but not for the autologous group.

Results: Twenty-six patients with CD20+ NHL (follicular=8, diffuse large cell=16, mantle = 2) were enrolled to receive autologous SCT. Median age was 53 years. Median prior treatments was 2. At transplant, 12 were in complete remission (CR), 12 in partial remission (PR)(6 were PET +) and 2 patients had stable disease. All patients received rituximab during stem cell collection. Adverse events were similar to those with BEAM alone. Median time to granulocyte engraftment was 9 days and to platelet engraftment of >20,000/mm³ was 11 days. At a median follow-up time of 15 months, 2-year overall and disease-free survival rates were 92%, and 83%, respectively.

Seven patients were enrolled to receive NST (follicular=2, CLL/SLL 3, diffuse large cell=1, mantle=1). Median age was 56 years. At transplant, 5 were in PR, 1 in CR and 1 had progressive disease. Three patients received 0.2 mCI/kg of ⁹⁰Y ibritumomab tiuxetan with their chemo-conditioning, and 4 patients received 0.3 mCI/kg. Peripheral blood from HLA-compatible siblings was the source of graft. Median times to granulocyte and platelet engraftment of >20,000/mm³ were both 12 days. One patient died of progressive disease, and one of infection/GVHD. Five patients remain alive in CR, at a median follow-up time of 16 months. At present, the study is ongoing at the higher dose level of 0.3 mCI/kg of ⁹⁰Y ibritumomab tiuxetan.

Conclusions: The combination of ⁹⁰Y ibritumomab tiuxetan at 0.4mCI/kg with BEAM is safe and effective in NHL patients undergoing autologous SCT. Randomized trials of autologous SCT with or without ⁹⁰Y ibritumomab tiuxetan are warranted. Further studies are needed to explore its role in NST.