Efficacy and Safety of a Single-Course of Yttrium-90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in Patients with Relapsed or Refractory Mantle Cell Lymphoma (MCL) After/Not Appropriate for Autologous Stem Cell Transplantation (ASCT) - A Phase II Trial of the European MCL Network.

Radioimmunotherapy (RIT) has demonstrated high clinical efficacy in the treatment of B-cell non-Hodgkin’s lymphoma (B-NHL) and has been approved for relapsed indolent and transformed B-NHL. However little is known about RIT with Zevalin® in patients with mantle cell lymphoma (MCL), a lymphoma subtype characterized by indolent morphology but aggressive clinical course with a median survival of only 3– 4 years and virtually no long-time survivors. Patients with relapsed or refractory CD20 positive MCL after/not appropriate for ASCT, WHO performance status <2, age < 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. Patients were excluded if they had > 25% bone marrow involvement, prior allogeneic stem cell transplantation or RIT, known CNS lymphoma, HIV infection or other concurrent severe medical disease. Patients with normal platelet counts received a dose of Zevalin® at 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. Currently, 14 patients have been enrolled and 6 are eligible for evaluation of treatment response. The median age was 68 years (range 56 – 71), 9 patients were male. All patients had been previously treated with Rituximab containing regimens. The median number of prior regimens was 4 (range 2–6). Zevalin® treatment was generally well tolerated, with the most common toxicities being hematologic. Thrombocytopenia grade 3 and 4 was observed in 2 and 4 patients, respectively, without significant bleeding complications. Granulocytopenia grade 3 and 4 occurred in 3 and 2 patients, respectively and 1 patient developed a grade 4 infectious complication. This patient also developed non-hematologic toxicities grade 3 and 4 consisting of sepsis-associated hepatotoxicity, diarrhoea and pleural empyema. Partial responses were observed in 2 of 6 patients (33.3 %), another patient experienced a stable disease. Median progression free survival (PFS) was 3.9 months in this high risk group. Preliminary analysis suggests that patients with bulky disease did not respond to radioimmunotherapy. The clinical course of the total group of this ongoing trial will be presented at the meeting. The observed responses to Zevalin® in heavily pretreated patients with MCL are promising, however median PFS was short-lived. Thus, a prior debulking strategy with combined immuno-chemotherapy is recommended to potentially achieve a longer duration of remission. Accordingly, in future trials RIT should be applied earlier in the treatment algorithm of MCL.