Pivotal Phase III Trial of Two Dose Levels of Denileukin Diftitox for the Treatment of Cutaneous T-Cell Lymphoma

Abstract

Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

“…72 Six of the 14 patients treated at the lower dose achieved a response, with 3 CRs (either CR or CCR). However, CRs only occurred in patients with stage I disease.…”

“…The median duration of response for all patients in the study was 6.9 months (range 2.7-46.1). 72 In addition, there was no clear indication of any dose response relationship. Routine premedication with systemic corticosteroids was prohibited in this study.…”

“…71 Steroid pretreatment was also correlated with an increase in the overall response rate(ORR): 60% of patients responded to therapy compared with 30% in the original phase III trial. 71,72 10.…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Denileukin diftitox is a fusion protein comprised of human IL-2 fused to a truncated diphtheria toxin which has high affinity for the IL-2 receptor and is internalized upon receptor binding, leading to liberation of the toxin and the induction of apoptosis. Phase I/II studies demonstrated objective responses in approximately one-third of patients [237][238][239], leading to a phase III study which randomized 71 patients with CD25 positive (i.e., 20% T cells positive by immunohistochemistry) CTCL, most with advanced-stage disease, to either 9 or 18 lg/kg/day of Dd given intravenously on five consecutive days every 3 weeks for up to eight cycles [240]. An objective response, 20% partial and 10% complete, was observed in 30% of patients, while an additional 32% of patients had stable disease.…”

“…Of note, Dd should not be administered in a facility ill equipped to provide cardiopulmonary resuscitation. Severe and persistent transaminitis, thyrotoxicosis, loss of visual acuity or color vision, and rhabdomyolysis have been reported but are uncommon [240,[246][247][248]. Investigations combining Dd with conventional chemotherapeutic agents are ongoing.…”