Denileukin Diftitox Improves QOL in Responding Patients With CTCL

Patients with relapsed or refractory (R/R) cutaneous T-cell lymphoma (CTCL) who responded to denileukin diftitox-cxdl (Lymphir) experienced sustained improvements in skin-related quality of life (QOL), according to exploratory patient-reported outcomes from the pivotal Study 302 (NCT01871727).¹

Among patients with stage I–III CTCL who responded to treatment, improvements in skin-related QOL were observed across assessments, with changes in overall QOL also favoring responders over nonresponders. Additionally, approximately one-third of heavily pretreated patients with clinically significant pruritus at baseline experienced a clinically meaningful reduction in itch severity. Findings were presented at the 2026 European Organisation for Research and Treatment of Cancer Cutaneous Lymphoma Tumour Group (EORTC-CLTG) Annual Meeting in Berlin, Germany.

"CTCL is a disease of the skin which symptomatic patients must deal with 24/7. Painful, itchy lesions take a real toll on their well-being," Myron Czuczman, MD, chief medical officer of Citius Oncology, stated in a news release. "In Study 302, patients who responded to denileukin diftitox reported sustained [QOL] improvements, and nearly a third of heavily pretreated patients with significant itch noted its decrease. We believe these findings underscore how important [QOL] considerations are as practitioners choose between various treatment options for their patients with relapsed or refractory CTCL."

About Denileukin Diftitox

Denileukin diftitox is an interleukin-2 receptor-directed cytotoxin indicated for adults with R/R stage I–III CTCL following at least 1 prior systemic therapy. The recombinant fusion protein combines an IL-2 receptor-binding domain with diphtheria toxin fragments, enabling it to bind IL-2 receptors on cells and inhibit protein synthesis, resulting in cell death. The agent has also demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes and exert direct cytotoxic activity against IL-2 receptor-expressing tumor cells.

QOL Improvements With Denileukin Diftitox

In the primary analysis set of 69 patients with stage I–III CTCL, 25 achieved a response to treatment. Among responders, mean changes from baseline in Skindex-29 Total Score ranged from −5.38 to −13.69 points across assessments, compared with minimal changes among nonresponders. Improvements were consistent across the instrument's 3 domains: symptoms, emotions, and functioning. Findings were similar in the full analysis set of 81 patients with stage I–IV disease.

Overall QOL, measured using the Functional Assessment of Cancer Therapy–General (FACT-G), also favored responders. At the end of treatment, mean FACT-G Total Score increased by 3.21 points among responders, compared with a decrease of 2.28 points among nonresponders.

Among 41 heavily pretreated patients with baseline pruritus scores of at least 20 mm on a 100-mm visual analog scale, 13 (32%; 95% CI, 18.1%-48.1%) experienced a clinically meaningful improvement, defined as a reduction of at least 20 mm sustained for 4 weeks or longer.

About Study 302

Study 302 was an open-label, single-arm, multicenter registrational trial that supported the FDA approval of denileukin diftitox for adults with R/R stage I–III CTCL following at least 1 prior systemic therapy.² Participants received denileukin diftitox at 9 μg/kg as a 1-hour intravenous infusion on days 1 through 5 of each 21-day cycle, for up to 8 cycles.

Health-related quality of life was an exploratory study objective, evaluated using 2 validated patient-reported outcome instruments: the disease-specific Skindex-29 and the general FACT-G. Pruritus was assessed separately using the VAS.

The exploratory findings add patient-reported outcomes to the clinical data supporting denileukin diftitox in previously treated CTCL, highlighting the potential relevance of treatment-associated symptom and quality-of-life changes alongside conventional measures of clinical response.

REFERENCES

1. Citius Oncology's Positive Quality of Life Data for LYMPHIR® (denileukin diftitox-cxdl) in Relapsed or Refractory Cutaneous T-Cell Lymphoma Presented at Premier Global CLTG Congress in Europe. News release. Citius Oncology. November 4, 2026. Accessed November 9, 2026. https://tinyurl.com/4uz7t4pk

2. A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma. ClinicalTrials.gov. Updated November 13, 2024. Accessed November 9, 2026. https://clinicaltrials.gov/study/NCT01871727