Combination therapy with pentostatin and cyclophosphamide for advanced refractory cutaneous T cell lymphoma (CTCL)

Abstract

6713 Background: CTCL comprises a spectrum of diseases of mature CD4+ T-lymphocytes. While a number of therapies, including cytokines, retinoids, and IL-2 receptor targeted agents, have demonstrated activity in patients with advanced and refractory disease, response durations have been short and no therapy has thus far demonstrated a survival benefit. Single agent therapy with purine analogs in patients with advanced disease has been reported, with response rates ranging from 20–30% for fludarabine and cladribine to 50–60% with pentostatin. Recent studies have demonstrated that the combination of alkylating agents with purine analogs is tolerable and may be associated with enhanced efficacy in patients with B-CLL and low grade B-NHL. Methods: We conducted a pilot study of the combination of pentostatin (3 mg/m2 daily x 3) with cyclophosphamide (600 mg/m2 on day 1) every 21 days in patients with advanced and refractory CTCL. Of six patients enrolled, all had failed multiple therapies including denileukin diftitox and bexarotene. Three had tumor stage disease (IIB), two had diffuse erythroderma (IIIB), and one had visceral involvement with a lung nodule (IVB). Three of these patients had Sezary syndrome. Results: Four of six patients responded, with three complete and one partial response. One patient had progressive disease and one discontinued therapy after two cycles due to dyspnea possibly related to pentostatin. Two of the patients with Sezary syndrome had complete and partial response, respectively, while the third had progressive disease. Response durations in the complete responders were 17 months, 29+ months, and 10 months in one patient who was consolidated with an allogeneic bone marrow transplant while in remission. The regimen was well-tolerated and no patient experienced grade IV hematologic toxicity. Conclusions: The combination of pentostatin and cyclophosphamide is active and well-tolerated in patients with advanced and refractory CTCL. This regimen should be further investigated in a phase II trial. No significant financial relationships to disclose.