A phase II study to evaluate the combination of fludarabine, mitoxantrone and dexamethasone (FMD) in patients with follicular lymphoma

Background: 'Molecular response' is being investigated as a therapeutic goal in follicular lymphoma (FL). High response rates in FL with the fludarabine combination 'FMD' have been associated with 'molecular remission'. A phase II study of FMD in FL was therefore conducted. Patients and methods: Fifty-four patients, ten of whom were newly diagnosed received FMD. Forty-four percent of the previously treated patients had 'chemoresistant' disease. Treatment comprised: fludarabine 25 mg/m² days 1-3, mitoxantrone 10 mg/m² day 1, and dexamethasone 20 mg days 1-5. Blood/bone marrow was collected for quantitation of t(14;18) by 'real-time' PCR. Results: The overall response rate was 37 of 54 (69%), complete responses being seen in 11 patients (20%), with no difference between newly diagnosed and the previously treated patients. However, the response rate in 'chemosensitive' relapse was 84%, compared to 44% in patients in whom the last prior regimen had failed. Molecular responses were seen in 17 of 25 and PCR negativity in 8 of 25, although molecular and clinical responses did not always correlate. Toxicity was moderate, 19 patients required admission. However, in 6 of 12 patients, subsequent G-CSF mobilised stem cell harvests failed. Conclusions: FMD was well tolerated but with a lower than expected response rate. Molecular responses were seen in the majority of responding patients however, 'molecular remission' was rare.