Efficacy and Safety of a Single-Course of Yttrium-90 Ibritumomab Tiuxetan for Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma after/not Appropriate for Autologous Stem Cell Transplantation - Final Analysis of a Phase II Trial of the European MCL Network.

Radioimmunotherapy (RIT) has demonstrated promising efficacy in the treatment of indolent and transformed B-cell non-Hodgkin’s lymphoma (B-NHL) and Yttrium-90 (90Y) Ibritumomab Tiuxetan (Zevalin®) has been approved in the USA and EU accordingly. However little is known about RIT in patients (pts) with mantle cell lymphoma (MCL), a lymphoma subtype characterized by indolent morphology but aggressive clinical course with a median survival of 3–4 years and virtually no long-term survivors. Patients with relapsed or refractory CD20 positive MCL after/not appropriate for autologous stem cell transplantation (ASCT), WHO performance status <2, age >18 and < 75 years and adequate function of the bone marrow (ANC >1,500/mm3, platelets >100,000/mm3), liver and kidneys were eligible for this trial. Pts were excluded if they had > 25% bone marrow involvement, prior RIT or allogeneic stem cell transplantation, known CNS lymphoma, HIV infection or other concurrent severe medical disease. Pts with pretreatment platelet counts >150,000/mm3 received a dose of 14.8 MBq 90Y/kg (to a maximum dose of 1,184 MBq), whereas those with platelet counts <150,000/mm3 received 11.1 MBq 90Y/kg. After presenting an interim analysis in 2006 a protocol amendment was approved by the authorities and EC to use RIT as consolidation therapy rather than a single-course regimen. A final analysis of the 19 patients that have been treated accordingly to the original protocol will be presented at the meeting. Currently data from 14 patients are evaluable. The median age was 67 years, 13 pts were >60 years, (56–76), 8 pts were male. The median number of prior regimens was 4 (1–5), all pts had been previously treated with rituximab (R) containing regimes. Treatment was generally well tolerated, with the most common toxicities being hematologic. Thrombocytopenia grade 3 and 4 was observed in 3 and 5 pts, respectively, without significant bleeding complications. Granulocytopenia grade 3 and 4 occurred in 3 pts, respectively, with 1 case of a grade 4 infectious complication. This pt also developed non-hematologic toxicities grade 3 and 4 consisting of sepsis-associated hepatotoxicity, diarrhea and pleural empyema. Objective responses were observed in 5 pts (35.7%), including 2 CR/CRu and 3 PR. Another pt experienced NC. Median progression free survival (PFS) was 3.8 months (115 days), median overall survival (OS) 19.4 months (582 days). The observed responses to Zevalin® in these heavily pretreated pts with MCL demonstrate antilymphoma activity however median PFS and OS were short-lived. Thus RIT in MCL may be an interesting option within a multimodal therapeutic concept, e.g. as consolidation therapy or as part of a myeloablative regimen. Both approaches are currently being evaluated in clinical trials by the European MCL Network.