We previously reported the results of a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus radioimmunotherapy (RIT) [FLUMIZ (Fludarabine, Mitoxantrone, Zevalin) trial], demonstrating that this combination was safe and very effective in untreated patients with follicular non-Hodgkin lymphoma. We are now providing long term efficacy and toxicity results of this combination strategy.
Sixty-one patients with stage III and IV untreated follicular lymphoma were enrolled between June 2004 and April 2006, at 13 Italian institutions. Briefly, treatment schedule was the following: oral fludarabine 40 mg/m2 on days 1–3, intravenous mitoxantrone 10 mg/m2 on day 1 every 28 days for six cycles, followed by one course of yttrium-90 (90Y)-labelled ibritumumab tiuxetan (Zevalin), which consisted in two weekly infusions of Rituximab 250 mg/m2 followed by a weight based dose of 90Y-ibritumumab tiuxetan. Primary endpoints at the time of the first analysis were complete response and hematological toxic effects, secondary endpoints were overall survival (OS) and progression free survival (PFS). Fifty-seven patients were treated with RIT after the completion of six courses of fludarabine and mitoxantrone (FN) regimen. Four patients were excluded because of disease progression (n=1) and bone marrow infiltration > 25% (n=3) at the end of the FN regimen. Median follow up at the time of the last analysis was 52 months (range 24–75). Five-year PFS was estimated to be 68%, 5-year OS was estimated to be 93.0%. Noteworthy, late hematological side effects such as myelodisplastic syndromes or acute myeloid leukemias have not been observed so far. All patients had a complete hematological recovery after the completion of the sequential treatment. 16 patients relapsed during the follow-up period and 4 patients died due to disease progression. 22 patients (38%) are in first complete remission after more than 4 years of follow-up. All relapsed patients underwent second line chemotherapy and high dose chemotherapy with stem cell rescue was performed in 4 patients.
These results confirm the long term efficacy and safety of 6 cycles of fludarabine and mitoxantrone followed by consolidation with 90Y-ibritumumab tiuxetan: the 5-year PFS and OS compare favourably with the results of chemoimmunotherapy alone in untreated follicular lymphoma, with no increased incidence of secondary hematologic malignancie
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.