Phase II Study of Denileukin Diftitox (Ontak) for Relapsed/Refractory T-Cell Non-Hodgkin’s Lymphoma.

Denileukin diftitox (ONTAK) is a fusion protein combining interleukin-2 (IL-2) and the enzymatically active domain of diphtheria toxin that targets tumor cells expressing the IL-2 receptor. We initiated a phase II study at MD Anderson Cancer Center to evaluate its efficacy in relapsed/refractory T-cell lymphoma excluding CTCL. Denileukin diftitox was administered at 18 mcg/kg/day by IV infusion daily for 5 days every three weeks for up to 8 cycles. Corticosteroid was given before every infusion to reduce the incidence and severity of acute hypersensitivity reaction. Twenty-five patients are currently evaluable for response. Median age was 55 years (range 26–80) and mean number of prior treatments was 2 (range 1–6). Tumor CD25 status was determined by flow cytometry and/or immunohistochemistry, with CD25 positivity being defined as 10% or more tumor cells expressing detectable CD25. Of the 13 patients with CD25+ T-cell lymphomas, there were 4 CR (30.8%) and 4 PR (30.8%) for an overall response rate of 61.6%. Of the 10 patients with CD25- tumors, there were 1 CR (10%) and 3 PR (30%) for an overall response rate of 40%. Two patients had a tumor CD25 of undetermined status. The overall response rate was 48% with 5 CR (20%) and 7 PR (28%). The median progression-free survival for responding patients was 6 months (range, 1–24+ months), with 1 patient with CD25+ ALK-1 negative ALCL having an ongoing CR at 24+ months. Of note is the fact that one patient who experienced a CR and another who had a PR went on to receive allogeneic transplantations while in remission induced by denileukin diftitox. Treatment was well tolerated, with the majority of toxicity being grade 1or 2 and transient. Most common toxicities seen were transient transaminase elevation, hypoalbuminemia and edema. Denileukin diftitox has activity in relapsed/refractory T-cell NHL, and is well tolerated at the dosing scheduled tested. While response to denileukin diftitox is seen in both CD25+ and CD25− T-NHL, drug activity in CD25 expressing tumors is particularly striking.