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

Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):467-74. doi: 10.1016/j.clml.2011.04.009. Epub 2011 Jun 22.

Abstract

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 (90)Y-ibritumomab tiuxetan (Zevalin) followed by maintenance rituximab (375 mg/m(2) weekly × 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 (90)Y-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 (90)Y-ibritumomab tiuxetan consolidation and rituximab maintenance is well tolerated, improving CR rates and maintaining durable responses in patients with untreated indolent lymphomas.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphoma, B-Cell, Marginal Zone / drug therapy*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, B-Cell, Marginal Zone / radiotherapy*
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / pathology
  • Lymphoma, Follicular / radiotherapy*
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Radiopharmaceuticals / therapeutic use
  • Rituximab
  • Survival Analysis
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • Rituximab
  • ibritumomab tiuxetan
  • Mitoxantrone
  • Vidarabine
  • fludarabine