title: 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.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rush University Medical Center, Chicago, IL 60612, USA. reem_karmali@rush.edu
authors.forename: Reem
authors.initials: R
authors.lastname: Karmali
authors.forename: Mohamad
authors.initials: M
authors.lastname: Kassar
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Venugopal
authors.forename: Jamile M
authors.initials: JM
authors.lastname: Shammo
authors.forename: Henry C
authors.initials: HC
authors.lastname: Fung
authors.forename: Robert
authors.initials: R
authors.lastname: Bayer
authors.forename: Teresa
authors.initials: T
authors.lastname: O'Brien
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Gregory
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D000069283:Rituximab; D016019:Survival Analysis; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine