Expert Insights: FDA Approval of Lymphir for Cutaneous T-Cell Lymphoma

Dr. Myron Czuczman highlighted the significance of the recent U.S. Food and Drug Administration (FDA) approval of Lymphir (denileukin diftitox-cxdl) for patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) in an interview with CURE.

He explained that Lymphir is an immunotoxin combining IL-2 with diphtheria toxin, which targets malignant T cells and regulatory T cells, allowing the immune system to attack tumors more effectively.

Clinical trials showed a 36% objective response rate in patients who had received at least one prior systemic therapy, with some achieving complete remission and others experiencing stable disease for six months or longer. Responses are not reduced by prior treatments, and most side effects, including infusion reactions and mild liver enzyme elevations, were manageable. Patients may also experience rapid relief from severe itching, often within the first cycle.

Czuczman is a physician-scientist and academic oncologist who practiced medicine for over 20 years at Roswell Park Comprehensive Cancer Center.

CURE: For patients who are newly diagnosed or living with cutaneous T-cell lymphoma, how would you explain this disease and why it can be especially difficult to treat over time?

Czuczman: Cutaneous T-cell lymphoma is essentially a condition where some T cells in the body become malignant or cancerous, and for some reason, they tend to go to the skin initially. Newly diagnosed patients often have small areas that appear to be a rash until a biopsy reveals the cancerous T cells.

When patients are first diagnosed, they can often be treated with what we call skin-directed therapies because the affected area is small. These therapies can include topical salves or even localized radiation. However, over time, these cells often spread to larger areas of skin, and in some cases, internally to the blood, lymph nodes or other organs.

The problem with this disease is that the only potential cure is an allogeneic stem cell transplant, which requires a suitable donor. This is rare, especially because the disease primarily affects older patients who are often ineligible for transplants. Most therapies available today help control the disease or put it in remission for a time, but the disease remains incurable.

Can you explain what this approval means for patients who have already tried other treatments and what it could mean for their care?

With the recent availability of Lymphir as of early December 2025, patients now have another potential therapy for this incurable disease. Lymphir is somewhat unique compared with other available agents because it is an immunotoxin — it combines an IL-2 protein with diphtheria toxin.

It works by binding to IL-2 receptors, which are found primarily on malignant cutaneous T-cell lymphoma cells. It also binds to IL-2 receptors on regulatory T cells, or Tregs. This dual action is important because once the IL-2-diphtheria toxin protein binds to the receptor and is internalized, the diphtheria toxin kills the cancer cell. At the same time, it temporarily depletes Tregs, which allows the patient’s immune system to better attack the tumor.

What do we know from clinical studies regarding how well Lymphir works, and what should patients understand about potential side effects?

Lymphir was studied in clinical trials at several top cancer centers in the U.S. and Australia. In the registrational trial reviewed by the FDA, patients with relapsed or refractory CTCL who had received at least one prior systemic therapy had a 36% objective response rate, meaning a 50% or greater reduction in disease. Some patients achieved complete remission, and another 13% to 14% had stable disease lasting six months or longer. About half of patients saw some clinical benefit.

Importantly, Lymphir does not appear to have cross-resistance with other therapies, so prior treatments do not seem to reduce its effectiveness. In Japan, the same agent — called RemiToro — was approved for relapsed or refractory CTCL and peripheral T-cell lymphomas with similar response rates.

Regarding side effects, most were mild to moderate (grade 1 or 2) and reversible. Side effects were more common during the first cycles and decreased over time. One notable risk is capillary leak syndrome, which can cause temporary swelling, weight gain or mild blood pressure changes. Liver enzyme elevations and infusion reactions were also observed but were manageable with supportive medications. Lymphir is administered via a one-hour infusion, five days a week every three weeks until disease progression.

An additional benefit for patients is relief from severe itching, or pruritus, which can affect the skin, scalp and extremities. For those who respond, relief can occur quickly — typically within a median of 1.4 months, often during the first or second cycle of therapy.

How could the availability of Lymphir change the outlook for patients with CTCL?

The availability of Lymphir is significant because it offers patients with incurable disease a period of disease control and potential improvement in quality of life. It can relieve extreme itching that other treatments may not address and improve the appearance of skin lesions, which can be disfiguring and affect self-confidence.

Looking ahead, ongoing research may allow Lymphir to be combined with other agents to further improve response rates and lengthen remission periods, giving patients more time and better quality of life with their loved ones.

Transcript has been edited for clarity and conciseness.

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