Responses and molecular markers in patients with peripheral T-cell lymphoma treated on a phase II trial of depsipeptide, FK228

3061 Background: The histone deacetylase inhibitors (HDIs) are a class of differentiating agents undergoing clinical testing. Depsipeptide, FK228 (Gloucester and Fujisawa Pharmaceuticals), is an HDI with potent cytotoxic activity in vitro and in vivo and clinical activity in patients with T-cell lymphoma. Based on these observations, we are conducting a multi-institutional phase II trial for patients with cutaneous and peripheral T-cell lymphoma. Methods: Forty-nine patients have been enrolled into 4 cohorts distinguished by tumor histology and prior therapy. Depsipeptide is administered as a 4 hr infusion on days 1, 8, and 15 of a 28 d cycle with a starting dose of 14mg/m2. Responses in PTCL are measured using the Cheson criteria. Results: Responses have been observed in 5 of 19 patients enrolled with relapsed or refractory PTCL at the NCI. Complete responses were observed in 2 patients; one in a patient with PTCL, unspecified, and anther with ALK-/CD30+ anaplastic large cell lymphoma. Partial responses in 3 patients were observed; 2 with PTCL, unspecified, and another with enteropathy-associated T-cell lymphoma. One patient recently enrolled with PTCL, unspecified, has completed 3 cycles with reduction of lesions on follow-up CT scan, that have not reached criteria for PR. Durations of response range from 8–14 months, with one patient continuing in CR at 14 months. Of these 19 patients, 5 had previously undergone autologous stem cell transplant, 2 of whom achieved a response with depsipeptide. Tumor cells were detected in the circulation of 7 patients and 2 had bone marrow involvement. Increased histone H3 acetylation has been observed by immuno-dot blot assay using GAPDH as a control in peripheral mononuclear cells obtained 4 or 24 hrs after initiation of treatment. Inductions ranging from 2 to 14-fold were observed in samples obtained from 10 of 14 patients. Conclusions: Depsipeptide as a single agent appears to have significant activity in patients with PTCL and combination therapy with depsipeptide should be pursued for this disease. All 4 cohorts remain open to accrual at the NCI and extramural sites. No significant financial relationships to disclose.