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.

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Francine Foss, MD, discusses the FDA approval of denileukin diftitox for the treatment of patients with CTCL.

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In today’s episode, supported by Citius Pharmaceuticals, we had the pleasure of speaking with Francine Foss, MD, to discuss the FDA approval of denileukin diftitox-cxdl (Lymphir) for the treatment of patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL) who have received 1 or more prior systemic therapies. Dr Foss is a professor of medicine (hematology) and dermatology and the director of the Multidisciplinary T Cell Lymphoma Program at the Yale School of Medicine, as well as the scientific leader of Lymphoma CRT at Yale Cancer Center in New Haven, Connecticut. 

 for the treatment of patients with relapsed/refractory CTCL who have received at least 1 prior systemic therapy. This regulatory decision was supported by findings from the phase 3 Study 302 (NCT01871727), in which patients who received the agent (n = 69) achieved an objective response rate of 36.2% (95% CI, 25.0%-48.7%) per independent review committee assessment, including a complete response rate of 8.7%.

In our exclusive interview, Dr Foss discussed the significance of this approval, key efficacy and safety data from Study 302, and her excitement about reintroducing an agent to the CTCL treatment paradigm that can induce particularly robust responses.

That’s all we have for today! Thank you for listening to this episode of 

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Dr Foss discusses the significance of the FDA approval of denileukin diftitox for patients with relapsed/refractory CTCL.

FDA Approval Insights: Denileukin Diftitox in Relapsed/Refractory CTCL

Francine Foss, MD, professor of medicine, Yale School of Medicine, discusses pursing new therapeutic options for the treatment of patients with T-cell non-Hodgkin lymphoma (NHL).

Although more than 60% of patients with aggressive T-cell NHL achieve a complete remission (CR), the rest have primary refractory disease and cannot move on to undergo transplant without additional therapy, according to Foss. Newer agents are under investigation to address this need, Foss says. For example, the incorporation of oral therapy in this setting could be promising, as most patients have already received aggressive chemotherapy, Foss adds.

Furthermore, those who relapse, either later in the course of their disease or if they have not undergone transplant, need additional therapy options. Allogeneic stem cell transplant or CAR T-cell therapies can be utilized to cure some of these patients, Foss says. It is important to pursue effective therapies that can induce CRs, even in the relapsed and refractory settings, Foss concludes.

Francine Foss, MD, discusses pursing new therapeutic options for the treatment of patients with T-cell non-Hodgkin lymphoma.

Dr. Foss on Pursuing New Therapeutic Options in T-Cell Non-Hodgkin Lymphoma 

Francine Foss, MD, professor of medicine and dermatology at Yale School of Medicine, discusses the challenges faced in cutaneous T-cell lymphoma.

It has been a great challenge to find effective therapies for patients with cutaneous T-cell lymphoma, says Foss. Oftentimes it is difficult to conduct clinical trials because there are so few patients with the disease, adds Foss. Without enough patient enrollment on these trials, it is difficult to get investigational drugs approved by the FDA.

However, the international, randomized MAVORIC phase III study managed to enroll almost 400 patients with cutaneous T-cell lymphoma. In the trial, investigators compared the use of mogamulizumab-kpkc (Poteligeo) with standard treatment with vorinostat in patients with previously treated cutaneous T-cell lymphoma. Data from this trial led to the September 2018 FDA approval of the drug for use in 2 rare types of cutaneous T-cell lymphoma: mycosis fungoides and Sézary syndrome. It took an international effort to conduct this trial, says Foss.

It’s important to remember that no matter how many drugs are available, patients will still progress and require additional therapy; this is a large unmet need in cutaneous T-cell lymphoma, concludes Foss.

Francine Foss, MD, discusses the challenges faced in cutaneous T-cell lymphoma.

Francine Foss, MD

Articles

Dr Foss on the FDA Approval of Denileukin Diftitox for CTCL

FDA Approval Insights: Denileukin Diftitox in Relapsed/Refractory CTCL

Dr. Foss on Pursuing New Therapeutic Options in T-Cell Non-Hodgkin Lymphoma

Dr. Foss on the Unmet Need in Cutaneous T-cell Lymphoma