An Improved Therapeutic for Cutaneous T-Cell Lymphoma

Limited treatment options are available for advanced-stage cutaneous T-cell lymphoma (CTCL). From 1999 to 2014, the fusion protein denileukin diftitox (DD) was available in the U.S. for CTCL treatment but then was withdrawn and reformulated to improve purity and bioactivity. Investigators now report on the reformulation, DD-cxdl, which, like its predecessor, links diphtheria toxin fragments to interleukin 2 (IL-2) and then binds to tumor cells expressing the IL-2 receptor, with subsequent intracellular toxin release and tumor-cell death.

In this multicenter, phase 3, single-arm registrational trial, 69 patients with relapsed or refractory stage IA–IIIB mycosis fungoides or Sézary syndrome and at least one prior systemic therapy received DD-cxdl (9 μg/kg/d intravenously on 5 consecutive days in 21-day cycles for 8 cycles). Those with a response (measured in skin, blood, lymph nodes, and viscera) could continue longer.

Patients had a median age of 64 years (range, 28–87) and a median of four prior systemic therapies (range, 1–18). The overall response rate (primary endpoint) was 36.2%, with complete responses in 8.7%; treatment responses occurred within 2 months, and median response duration was 8.9 months. More than 80% of patients had cutaneous responses, with about half showing at least a 50% decrease in skin lesions. Infusion reactions occurred in 74% of patients (almost all grade 1/2 and in the first 2 cycles), hepatotoxicity in 36% (grade 3/4 in 4–9%), and capillary leak syndrome in 20% (most in the first 3 cycles; grade 3/4 in 6%). Five patients discontinued treatment due to toxicity.