FDA Approves Denileukin Diftitox for Relapsed/Refractory Cutaneous T-Cell Lymphoma

FDA Approves Denileukin Diftitox for Relapsed/Refractory Cutaneous T-Cell Lymphoma

The FDA approved denileukin diftitox-cxdl (Lymphir) for the treatment of patients with relapsed/refractory cutaneous T-cell lymphoma who received at least 1 prior systemic therapy.

This marks the first indication for this novel immunotherapy and the only treatment for cutaneous T-cell lymphoma that targets the IL-2 receptor, according to a press release from Citius Pharmaceuticals, the manufacturer of the therapy.

“Lymphir offers new hope for patients suffering from cutaneous T-cell lymphoma, a rare and chronic cancer characterized by debilitating skin lesions and severe itching,” Leonard Mazur, the Chief Executive Officer of Citius Pharmaceuticals, said in the release. “This approval is a significant milestone for [cutaneous T-cell lymphoma] patients. The introduction of Lymphir, with its potential to rapidly reduce skin disease and control symptomatic itching without cumulative toxicity, is expected to expand the [cutaneous T-cell lymphoma] treatment landscape.”

The FDA approval is based on findings from the phase 3 Pivotal Study 302 (NCT01871727), which included 69 patients with cutaneous T-cell lymphoma who previously received at least 1 systemic treatment. Of note, patients in this study previously received a median of 4 anticancer therapies (range, 1-18). These patients with stage I-III cutaneous T-cell lymphoma received denileukin diftitox at 9 μg /kg/day).

The primary efficacy outcome of this study was objective response rate assessed by an independent review committee. In particular, the objective response rate in this study was 36.2% (95% CI, 25.0-48.7), with a complete response rate of 8.7%.

The median time to response with denileukin diftitox was 1.41 months, with approximately 70% of patients achieving a response to therapy after 1 to 2 cycles of the therapy. More than half of patients (52%) had a duration of response of at least 6 months. In addition, 84.4% of patients whose skin was evaluable during the study had a decrease in skin tumor burden, with 12.5% of patients achieving a complete clearing of skin disease.

An exploratory endpoint of this study was pruritus, and 31.7% of patients had a clinically significant improvement. According to the release, no cumulative toxicities were observed in patients treated with Lymphir.

"As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with [relapsed/refractory cutaneous T-cell lymphoma],” said Dr. Francine Foss, professor of hematology and director of the multidisciplinary T-cell lymphoma program at Yale Cancer Center in New Haven, Connecticut, said in the release. “Given the long-term nature of the disease, pruritus, ulceration of the tumors, and secondary pyogenic skin infection, it is vital to get this skin involvement under control. Lymphir is the first therapeutic option in many years to offer hope of reducing skin disease, bringing us one step closer to filling the need for [cutaneous T-cell lymphoma] patients, particularly those that are not able to complete or continue prior therapies.”

The safety profile of denileukin diftitox was similar to what is known with the therapy, according to the release. In 3 studies of 119 patients with cutaneous T-cell lymphoma treated with 9 μg of denileukin diftitox, the most common adverse reactions, occurring in at least 20% of patients, included decreased albumin levels, increased transaminases levels, edema, nausea, fatigue, decreased hemoglobin levels, rash, musculoskeletal pain, constipation, chills, capillary leak syndrome, and pyrexia.

The prescribing information for denileukin diftitox includes a boxed warning for capillary leak syndrome, and that patients should be monitored for signs and symptoms during treatment. The warning also notes that denileukin diftitox should be withheld until capillary leak syndrome resolves, or permanently discontinue the treatment based on severity.

There is also a postmarketing requirement from the FDA asking Citius to characterize the risk for visual impairment in patients with cutaneous T-cell lymphoma treated with denileukin diftitox.

“We believe Lymphir’s unique IL-2 receptor-targeted treatment, which kills tumor cells directly, and concurrently depletes host Tregs in order to boost the body's immune response, is an important differentiator and offers clinically meaningful benefits to a significant percentage of [relapsed/refractory] patients,” Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals, said in the release.

Reference

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