Fludarabine + Cyclophosphamide + Mitoxantrone + Rituxan
Fludarabine 25 mg/m2/day days 1-3
Cyclophosphamide 200 mg/m2/day days 1-3
Mitoxantrone 8 mg/m2 day 1
Rituxan 375 mg/m2 day -1 (one day before chemotherapy)
Hiddemann et al Blood 98:84a, 2001
N= 147 Patients with refractory follicular (FL) & mantle cell lymphomas (MCL)
FCM+R: 95% ORR in (FL) 77% ORR (MCL); 36% CR, 53% PR
FCM: 68% ORR in (FL) 27% ORR (MCL); 15% CR, 38% PR
Treatment With Ibritumomab Tiuxetan Radio-immunotherapy in Patients With Rituximab-Refractory Follicular Non-Hodgkins Lymphoma
Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkins lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-na´ve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL.
PATIENTS AND METHODS: Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m2 weekly for 4 weeks) or time to progression (TTP) of 6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m2 intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients.
RESULTS: Fifty-seven patients were treated. The median age was 54 years, 74% had tumors 5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meierestimated TTP was 6.8 months (range, 1.1 to 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively.
CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.