Fludarabine, Mitoxantrone and Dexametasone in the Treatment of Relapsed and Refractory Low-Grade Non-Hodgkin Lymphoma.

The purpose of the study was to evaluate response, duration of response, and toxicity of fludarabine (F), mitoxantrone (M), and dexamethason (D) (FMD) in patients (pts) with relapsed or refractory low-grade non-Hodgkin lymphoma (LGNHL). 26 pts with advanced relapsed/refractory LGNHL exposed to previous chemotherapy (CHT) received 3–6 monthly cycles of FMD. The median age was 60 years (range 34–73), included 13 male (50%) and 13 female (50 %). The regimen consisted of F (25 mg/m² i.v., day 1–3), M (10 mg/m² i.v., day 1) and D (20 mg p.o., day 1–5). Parameters analyzed included response, toxicity and infection rates, number of previous CHT lines, performance status (ECOG), Ann Arbor scale, LDH, International Prognostic Index score, freedom from progression (FFP) and overall survival (OS). In total 78 cycles of FMD was administered. This induced 25% complete and 37,5% partial response, with a total response rate of 62,5%. After 14 months of the median follow-up of the pts remaining alive, median FFP was 11 months and median OS has not been achieved yet. Out of 78 administered cycles 16 (20%) were associated with toxicity, including 8 (10%) severe infections despite prophylaxis and 6 (8%) grade III/IV neutropenias. In addition, one case of grade III/IV thrombocytopenia and acute noninflammatory renal dysfunction were observed. Toxicity rate was not correlated with the number of previous CHT lines or ECOG, but IPI >2 was significant factor predictive for FMD-related toxicity (p=.037). Shorter OS was observed for the pts with ECOG>1 (p=.049), IPI>2 (p=.005) and FMD-related toxicity (p=.036). FMD is an active regimen for relapsed and refractory LGNHL. Toxicity rate is substantial and seems to predict survival.