⁹⁰y Ibritumomab Tiuxetan as Initial Treatment for Follicular Lymphoma (ZEUS Protocol). An Italian Cooperative Study Group

Background: Approximately 80% of patients with Follicular Lymphoma present with disseminated disease, which is consider incurable with standard treatment. Monoclonal antibodies labeled with radionuclides can potentially deliver cytocidal doses of radiation to all sites of disseminated disease. Anti-CD20 radioimmunotherapy has resulted effective in patients who have had relapse after chemotherapy or who have refractory. More recently, radioimmunotherapy (¹³¹I-Tositumomab) has been tested also in previously untreated patients with very good results (

Methods: This study is an open-label, prospective, phase II evaluation of efficacy and safety of a single course of ⁹⁰Y-ibritumomab tiuxetan at a standard dose of 15 MBq/kg (or 0.4 mCi/kg) in untreated follicular NHL patients. From February 2007, 27 patients with stage III–IV FL received at diagnosis a single course of treatment with ⁹⁰Y Ibritumomab Tiuxetan (registered as Zevalin). The drug for this study has been suppored by Bayer-Italy. Fifteen patients have enough follow-up for a first evaluation. Eligibility criteria were as follows: CD20 positive follicular lymphoma grade 1 or 2; an age of at least 18 years; no prior therapy, Ann Harbor stage III or IV; at least one bidimensional measurable lesion; involvement of 25% or less of the marrow by lymphoma on trephine biopsy and an absolute neutrophil and platelet count of >1.500×10³/ml and 100.000×10³/ml, respectively.

Results: Ninety-three percent (14/15 patients) of the patients had any response, and 73% (11/15 patients) had a complete remission. The use of PCR to detect rearrangement of the BCL2 gene was positive at diagnosis in 7/11 remitters patients; six out of these 7 patients developed molecular response and are in continuous complete remission 4–18 months (median, 9 months) after therapy. After a median follow-up of 10 months (range, 4–18 months), 14 patients (93%) are alive, of whom 10 patients in continous complete remission. One remitter patient died of brain stroke; the cause of death was not linked to Zevalin. No patient required hematopoietic growth factors. By week 4, seven patients developed grade 3 thrombocytopenia and 5 of them required platelet transfusions. Until now, no patient developed signs of MDS.

Conclusion: One single dose of ⁹⁰Y Ibritumomab Tiuxetan as initial treatment can induce clinical and molecular remission in patients with advanced untreated follicular lymphoma; moreover, hematological toxicity was low and quickly reversible.