Insights Into the Approval of Denileukin Diftitox-cxdl for Cutaneous T-Cell Lymphoma

The US Food and Drug Administration recently approved Citius Pharmaceuticals’ denileukin diftitox-cxdl (Lymphir) for adults with relapsed or refractory cutaneous T-cell lymphoma (CTCL).¹

The approval is based on positive phase 3 trial results showing effectiveness in CTCL stages I to III. The trial involved administering the drug intravenously over 5 consecutive days every 21 days, with primary outcomes focused on dose-limiting toxicities and overall response rate, and secondary outcomes including response duration and adverse events.

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Following the approval, Dermatology Times spoke with Myron Czuczman, MD, chief medical officer and EVP of Citius, to discuss the implications of the approval for dermatology clinicians and the role of a multidisciplinary care team in treating patients with CTCL.

Understanding Lymphir’s Mechanism of Action

Lymphir is an innovative agent classified as an immunotoxin, a fusion protein combining IL-2 with a potent toxin. Unlike other FDA-approved systemic targeted therapies for CTCL, Lymphir operates through a distinctive mechanism.

"What’s interesting about the mechanism of action is that it is unique, and it is different than other… FDA-approved systemic targeted therapies that are in the field. Our product is unique in its class," Czuczman said.

Lymphir is designed to target the IL-2 receptor, which is prevalent on T-cells in CTCLs. The IL-2 component binds to its receptor, while the fused toxin delivers a cytotoxic effect to the tumor cells.

"The value here is that as you give it in the body, it finds its place for the structures. These predominantly would be on these cancers, cutaneous T-cell lymphoma, which will be the indication in the United States in relapsed and refractive patients after one prior systemic therapy," Czuczman said.

Lymphir also transiently depletes regulatory T-cells (Tregs), which suppress the immune response against tumors.

Clinical Trial Results and Efficacy

The pivotal study for Lymphir demonstrated promising results. The primary endpoint, objective response rate (ORR), was 36% according to the independent review committee, with investigator-assessed rates slightly higher at 42%.

The study included heavily pre-treated patients, with a median of 4 prior therapies.

"What’s interesting also is that the duration of response was over 6 months," Czuczman said. "52% were over 6, and we still had about 20% of patients, we have these responders, and they go out to perhaps one year or more.”

In addition to the ORR, Lymphir showed a significant impact on skin tumor burden.

"What’s most noticeable is that it works quite quickly… Over 80% of patients that had skin disease had a decrease in their skin tumor burden," Czuczman noted. "About 50% had a decrease in baseline or greater, equal to 50% along with around 12, 13% complete remission."

Integration into Clinical Practice

"Dermatologists at large academic centers will often coordinate with hematologists, oncologists, and other specialists to manage these complex cases," Czuczman said. "In the past, interdisciplinary teams… including dermatologists, hematologists, oncologists, and radiation oncologists, have played a crucial role in patient care."

Czuczman concluded with gratitude for the approval, noting: "It’s very rewarding to see that we have an active agent that can help prolong patients’ survival, control their symptomatic diseases, and is just another important type of agent to use."

Reference

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. PR Newswire. August 8, 2024. Accessed August 13, 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