Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma

Authors

Francine M Foss
Youn H Kim
H Miles Prince
Oleg E Akilov
Christiane Querfeld
Lucia Seminario-Vidal
David C Fisher
Timothy M Kuzel
Costas K Yannakou
Larisa J Geskin
Tatyana Feldman
Lubomir Sokol
Pamela Blair Allen
Nam Hoang Dang
Fernando Cabanillas
Henry K Wong
Chean Eng Ooi
Dongyuan Xing
Nicholas Sauter
Preeti Singh
Myron Czuczman
Madeleine Duvic

Publication Date

4-1-2025

Journal

Journal of Clinical Oncology

DOI

10.1200/JCO-24-01549

PMID

39700456

PMCID

PMC11949209

PubMedCentral® Posted Date

12-19-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Patients and methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. The primary efficacy end point was objective response rate (ORR) using the Global Response Score. Secondary end points were duration of response (DOR), time to response (TTR), skin tumor burden, and safety and tolerability.

Results: The PEAS included 69 patients (median age, 64.0 years). The ORR was 36.2% (95% CI, 25.0 to 48.7), including 8.7% with complete response. The median DOR was 8.9 months (95% CI, 5.0 to not estimable), and the median (Q1-Q3) TTR was 1.4 (0.7-2.1) months. A total of 84.4% of patients showed decreased skin tumor burden, with 48.4% showing a ≥50% decrease. Treatment-emergent adverse events (TEAEs) of special interest, most of which were grade 1 or 2, included infusion reaction (73.9%), hypersensitivity (68.1%), hepatotoxicity (36.2%), and capillary leak syndrome (20.3% [grade ≥3, 5.8%]). Other common TEAEs were nausea (43.5%) and fatigue (31.9%).

Conclusion: Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL.

Trial registration: ClinicalTrials.gov NCT01871727.

Keywords

Humans, Diphtheria Toxin, Middle Aged, Male, Female, Interleukin-2, Aged, Lymphoma, T-Cell, Cutaneous, Recombinant Fusion Proteins, Adult, Skin Neoplasms, Aged, 80 and over, Antineoplastic Agents, Neoplasm Recurrence, Local

Published Open-Access

yes

Recommended Citation

Foss, Francine M; Kim, Youn H; Prince, H Miles; et al., "Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma" (2025). Faculty, Staff and Student Publications. 3047.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3047