FDA Approves Denileukin Difitox for Refractory Cutaneous T-Cell Lymphoma

The FDA announced their approval of deileukin diftitox-cxdl (LYMPHIR; Citius Pharmaceuticals) today for the use in adult patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL).¹ Deileukin diftitox is an immunotherapy treatment that can be used after at least 1 prior treatment. This approval marks the first indication for deileukin difitox.

CTCL is a chronic non-Hodgkin lymphoma that is rare and can affect patients severely. The skin cancer affects an estimated 40,000 people who live with the disease with approximately 2500 to 3000 new cases recorded each year. The cancer is not curable and there is no official treatment used across all instances and the treatment options are limited. The primary goal of treatment includes reducing and controlling skin plaques and itching through cycling through various skin therapies until the cancer is resistant. After this is achieved, systemic medicines are prescribed until the disease progresses again or toxicity occurs.

This FDA approval can be used to treat patients with relapsed and refractory cutaneous T-cell lymphoma | Image credit: Dr_Microbe - stock.adobe.com

Deileukin diftitox would offer another method of systemic therapy for patients to use for CTCL. The therapy aims to target and eliminate T-cells that are malignant all while making sure that healthy cells remain safe. IL-2 receptors found in T-cell lymphomas and Tregs are targeted using this treatment.

The phase 3 study 302 provided the evidence needed for this approval. The single-arm, multicenter trial study included patients with CTCL who were not treatment naïve and had a median (range) age of 64 years (28-87).² All participants needed to have an expression of CD25 that was 20% or higher of biopsied malignant cells by immunohistochemistry. The participants were primarily male (65%) and white (73%), with 19% identifying as African American, 1% as Asian, and 14% as Hispanic or Latino. A median of 4 (range, 1-18) prior therapies had been received by the patients involved. A total of 69 patients with stages I to III CTCL were treated with denileukin diftitox at 9 μg/kg/day dose. The objective response rate was found to be 36.2% (95% CI, 25.0%-48.7%); the complete response rate was 8.7%.

Response took a median of 1.41 months; 1 to 2 cycles of treatment were all that was needed for approximately 70% of responders to see results. A total of 52.0% of patients had at least 6 months of response duration and 84.4% of the patients had a decrease in their skin tumor burden, with 12.5% seeing a clearing of skin disease. Pruritis improvement was found in 31.7% of the patients. Toxicity was reported in none of the patients receiving denileukin diftitox.

Adverse reactions to the dose included transaminases, nausea, hemoglobin decrease, albumin decrease, musculoskeletal pain, edema, fatigue, chills, pyrexia, constipation, rash, and capillary leak syndrome. Hepatotoxicity can occur in patients as elevated alanine transaminase occurred in 70% of the patients.

“[Denileukin diftitox] offers new hope for patients suffering from cutaneous T-cell lymphoma, a rare and chronic cancer characterized by debilitating skin lesions and severe itching. This approval is a significant milestone for CTCL patients. The introduction of [denileukin diftitox], with its potential to rapidly reduce skin disease and control symptomatic itching without cumulative toxicity, is expected to expand the CTCL treatment landscape and grow the overall market,” Lenoard Mazur, the chief executive officer at Citius Pharmaceuticals, said in a press release.¹

References

1. Citius Pharmaceuticals receives FDA approval for LYMPHIR (denileukin diftitox-cxdl) immunotherapy for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma. News release. Citius Pharmaceuticals, Inc. August 8, 2024. Accessed August 8, 2024. https://www.prnewswire.com/news-releases/citius-pharmaceuticals-receives-fda-approval-for-lymphir-denileukin-diftitox-cxdl-immunotherapy-for-the-treatment-of-adults-with-relapsed-or-refractory-cutaneous-t-cell-lymphoma-302217630.html
2. Foss FM, Kim YH, Prince HMM, et al. Efficacy and safety of E7777 (improved purity denlieukin diftitox [ONTAK]) in patients with replased or refractory cutaneous T-cell lymphoma: results from pivotal study 302. Blood. 2022;140(Suppl 1):1491-1492. doi:10.1182/blood-2022-166916