Safety and Efficacy of Combination Therapy with Fludarabine, Mitoxantrone, and Rituximab Followed by Yttrium-90 Ibritumomab Tiuxetan and Maintenance Rituximab as Front-Line Therapy for Patients With Follicular or Marginal Zone Lymphoma

Better survival outcomes in indolent lymphomas are needed. 22 patients withfollicular/marginal zone lymphoma were enrolled in a phase II clinical trial to receive chemoimmunotherapy followed by radioimmunotherapy consolidation and rituximab maintenance. This regimen was safe, obtaining high complete remission rates and durable responses. This approach warrants further investigation as it may provide a survival advantage in indolent lymphomas. Background: We conducted a single-institution phase II clinical trial evaluating the safety and efficacy of combination chemoimmunotherapy followed by radioimmunotherapy consolidation and rituximab maintenance as front-line treatment in indolent lymphomas. Patients and Methods: We enrolled 20 patients with intermediate-to high-risk follicular lymphoma and 2 patients with marginal zone lymphoma. Treatment consisted of 4-6 cycles of FM (fludarabine 25 mg/m(2) on days 1-3, mitoxantrone 12 mg/m(2) on day 1 of each 28-day cycle). The protocol was amended after enrolling the first 4 patients to include rituximab 375 mg/m(2) on day 1. After 6-8 weeks, responders received Y-90-ibritumomab tiuxetan (Zevalin) followed by maintenance rituximab (375 mg/m(2) weekly x 4 doses, repeated every 6 months for 2 years). Results: After R-FM, the overall response rate was 95% with a complete response rate (CR) of 45% (n = 10), a partial response (PR) rate of 50% (n = 11), and stable disease in 1 patient. Nineteen patients received 90Y-ibritumomab tiuxetan with a 60% conversion rate of PR to CR, resulting in an improved CR of 79% (n = 15) and a PR of 21% (n = 4). Fifteen patients proceeded to rituximab maintenance resulting in 3 patients with PR converting to CR. At median follow-up of 49.6 months, median progression-free survival (PFS) was 47.2 months and median overall survival (OS) was not reached in an intent-to-treat analysis. The most common adverse effects were hematologic, with 2 patients experiencing treatment-related myelodysplastic syndrome (MDS), evolving to acute myelogenous leukemia (AML) in 1 patient. Conclusion: R-FM with Y-90-ibritumomab tiuxetan consolidation and rituximab maintenance is well tolerated, improving CR rates and maintaining durable responses in patients with untreated indolent lymphomas.