Fludarabine, Mitoxantrone Plus 90Y-Ibritumomab Tiuxetan Safe, Effective in Treatment-Naive Patients with Follicular Lymphoma

SAN DIEGO, CA—Investigators at the 53rd American Society of Hematology Annual Meeting and Exposition reported that long-term efficacy and toxicity of fludarabine and mitoxantrone followed by radioimmunotherapy with 90Y ibritumomab tiuxetan had six-year rates of progression-free survival (PFS) and overall survival (OS) that compared favorably with chemoimmunotherapy alone in patients with untreated follicular lymphoma (FL). Peri Guigi Zinzani, MD, PhD, of “L. and A. Seràgnoli,” Policlinico S.Orsola-Malpighi, University of Bologna, Bologna, Italy, and colleagues added that no increased incidence of secondary hematologic malignancies, such as myelodysplastic syndrome or acute myeloid leukemia, were observed.

A multicenter, nonrandomized Phase 2 trial previously had found that the FLUMIZ (fludarabine, mitoxantrone, 90Y ibritumomab tiuxetan) combination was safe and effective in untreated patients with follicular non-Hodgkin lymphoma, reported; in this study, long-term efficacy and toxicity results were evaluated. Between June 2004 and April 2006, 61 patients with stage III and IV untreated FL were enrolled at 13 institutions in Italy. Patients received oral fludarabine 40mg/m2 Days 1–3 and mitoxantrone 10mg/m2 IV on Day 1 every 28 days for six cycles, followed by one course of 90Y-ibritumomab tiuxetan, administered as two weekly infusions of rituximab 250mg/m2 followed by a weight-based dose of 90Y-ibritumomab tiuxetan. Primary endpoints were complete response and hematologic toxicity; secondary endpoints were OS and PFS. Following treatment with fludarabine and mitoxantrone, four patients were excluded, one due to disease progression and three due to bone-marrow infiltration >25%. The remaining 57 patients received 90Y-ibritumomab tiuxetan.

At the time of last analysis, median follow-up was 52 months (range 24–75). Six-year PFS was 68% and 6-year OS, 93%. All patients had complete hematologic recovery after completing the sequential treatment. During follow-up, 20 patients relapsed and four patients died due to disease progression. All of the patients who relapsed underwent second-line chemotherapy; high-dose chemotherapy with stem cell rescue was performed in four patients. After more than four years of follow-up, 22 patients (38%) remain in first complete remission. Dr. Zinzani and colleagues reported that the results of this follow-up study confirm the safety and long-term efficacy of six cycles of this combination regimen.