To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: FDA Approves Denileukin Diftitox for Patients With Recurrent Cutaneous T-Cell Lymphoma URL: http://www.pslgroup.com/dg/22EEBA.htm Doctor's Guide October 16, 2008
WOODCLIFF LAKE, NJ -- October 16, 2008 -- The US Food and Drug Administration (FDA) has approved denileukin diftitox (Ontak) solution for intravenous injection for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the interleukin (IL)-2 receptor (CD25+). A separate efficacy supplement that included data from patients with CTCL whose malignant cells did not test positive for the CD25 component of the IL-2 receptor received a complete response letter. The FDA's approval is based on data from a randomised, double-blind, placebo-controlled, phase 3 clinical trial that evaluated the overall efficacy and safety of denileukin diftitox in patients with refractory CTCL (stages Ia-III) whose malignant cells expressed the CD25 component of the IL-2 receptor. The study met its primary endpoint of overall response rate (ORR). The ORR was 46% for the 18-mcg/kg/day dose of denileukin diftitox (P = .002 vs placebo) and 37% for the 9-mcg/kg/day dose (P = .03 vs placebo) versus 15% for placebo. Progression-free survival (PFS), a secondary endpoint of the study, suggested a 73% reduction in risk of disease progression in the 18-mcg/kg/day group (P = .0002) and a 58% reduction in risk of disease progression in the 9-mcg/kg/day group (P = .02) compared with placebo. In the trial, 25% of patients treated with denileukin diftitox experienced a serious adverse event. The most common serious adverse events were capillary leak syndrome (4%), dehydration (4%), pyrexia (3%), hypotension (2%), skin disorder (2%), chest pain (2%), hypoalbuminaemia (2%), and fatigue (2%). Denileukin diftitox was discontinued in 20 patients due to 1 or more adverse events. The most common adverse events (>=10% of patients) were pyrexia, nausea, rigors, fatigue, vomiting, headache, peripheral oedema, diarrhoea, anorexia, rash, myalgia, cough, pruritus, back pain, asthenia, hypotension, upper respiratory tract infection, dizziness, arthralgia, pain, chest pain, dysgeusia, and dyspnoea. Serious infusion reactions, capillary leak syndrome, and loss of visual acuity have been reported: · Serious and fatal infusion reactions -- Administer denileukin diftitox in a facility equipped and staffed for cardiopulmonary resuscitation. Immediately stop and permanently discontinue denileukin diftitox for serious infusion reactions. · Capillary leak syndrome resulting in death -- Monitor weight, oedema, blood pressure, and serum albumin levels prior to and during treatment. Withhold treatment for serum albumin levels <3 g/dL. · Loss of visual acuity and colour vision -- Recovery was reported in some of the affected patients; however, most patients reported persistent visual impairment.