Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma: an interim analysis.

Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL.
Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles.
Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction.
Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.