Dr Foss on the FDA Approval of Denileukin Diftitox for CTCL

Francine Foss, MD, professor, medicine, Department of Medical Oncology, Yale School of Medicine, discusses the FDA approval of denileukin diftitox-cxdl (Lymphir) for the treatment of patients with cutaneous T-cell lymphoma (CTCL).

This approval is noteworthy, as denileukin diftitox, (previously Ontak), was removed from the market due to manufacturing issues, Foss begins. On August 8, 2024, the FDA approved a reformulated version of denileukin diftitox for the treatment of patients with relapsed/refractory CTCL who have received 1 or more prior systemic therapies. This reformulated agent has improved bioavailability, enabling its reintroduction for clinical use, Foss explains.

Denileukin diftitox is a recombinant fusion protein that combines interleukin-2 (IL-2) with CD25-targeting diphtheria toxin, a high-affinity component of the IL-2 receptor found on malignant T cells in CTCL. This targeted mechanism provides a distinct therapeutic option that addresses a receptor on the surface of CTCL cells, potentially minimizing off-target effects.

CTCL is a complex and challenging-to-manage malignancy with a prolonged disease course and limited curative options, according to Foss. Although there are several approved therapies for this disease, including skin-directed treatments, systemic retinoids, and histone deacetylase inhibitors, many patients experience disease relapse or progression, necessitating additional therapeutic strategies, she says. Foss highlights that patients with CTCL often undergo multiple lines of therapy over time, underscoring the continuous need for new, effective treatments that can be initiated as patients progress through their disease.

The approval of denileukin diftitox provides an important addition to the therapeutic arsenal for CTCL, Foss states. Given the drug’s targeted action, it is well suited for a subset of patients who express the CD25 marker, potentially offering a more tailored and efficient treatment approach. This agent’s mechanism of action also allows oncologists to strategically sequence it alongside other therapies, optimizing treatment outcomes in patients with recurrent or refractory disease, Foss explains. The return of denileukin diftitox to the CTCL treatment paradigm fills a critical gap in the management of this disease, particularly for patients who have exhausted other treatment options, Foss concludes.