FDA Approves Denileukin Diftitox-Cxdl for the Treatment of T-Cell Lymphoma

The FDA approved denileukin diftitox-cxdl (Lymphir; Citius Pharmaceuticals), a novel immunotherapy, for the treatment of relapsed or refractory (R/R) cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy. This is the only CTCL therapy that targets IL-2 receptors in malignant T-cells and Tregs and is the first indication for denileukin diftitox-cxdl.¹

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"As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with R/R CTCL," said Francine Foss, MD, professor of hematology and director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, in a news 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. [Denileukin diftitox-cxdl] 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 patients [with CTCL], particularly those that are not able to complete or continue prior therapies."¹

The approval was based on a multicenter, open-label study (NCT01871727) of the treatment for patients with recurrent or persistent CTCL, including an initial lead-in portion to choose the recommended dose for the main portion of the study, which was used to test efficacy. It included 3 phases: a pretreatment phase, treatment phase, and extension phase with a follow-up period.²

Denileukin diftitox-cxdl was administered intravenously over 60 minutes on 5 consecutive days over every cycle of 21 days, according to the clinical trial information. The primary end points included dose-limiting toxicities in the lead-in part of the study for 1 cycle of 21 days, maximum tolerated dose in the lead-in part for up to 12 months, and the overall response rate (ORR) in the main study from day 1 until disease progression or recurrence for up to 30 months. Secondary end points included duration of response (DOR), time to response (TTR), adverse events (AEs) and serious AEs, number of individuals with skin response in the main study, duration of skin response in the main study, and time to skin response in the main study.²

The investigators found that a dose of 9 mcg/kg/day had clinically meaningful efficacy for the patient population. According to authors of the study, a total of 112 individuals were enrolled in the study, with 21 in the lead-in and 91 in the main part. The median number of cycles that patients received was 6, and the ORR was 36.2% (reviewed by an independent review committee), with 8.7% achieving complete response. DOR was at least 6 months for 52% of responders and 12 months for 20% of responders. TTR was a median of 1.41 months, and the majority of responders had a response after 1 to 2 cycles, the study authors explained.³

The most common treatment-emergent AEs (TEAEs) included nausea, fatigue, and increased alanine aminotransferase, chills, and peripheral edema. The mean number of TEAEs per patient were higher in the first 1 to 2 cycles, then decreased and remained low or stable over the rest of therapy, according to the authors.³

Editor's Note: Updated at 11:23 am on August 8, 2024.

REFERENCES

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. Citius Pharma. August 8, 2024. Accessed August 8, 2024. https://prnmedia.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

2. A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma. ClinicalTrials.gov identification: NCT01871727. Updated December 12, 2022. Accessed August 8, 2024. https://clinicaltrials.gov/study/NCT01871727

3. Foss FM, Kim YH, Prince MM, Kuzel TM, et al. Efficacy and Safety of E7777 (improved purity Denileukin diftitox [ONTAK]) in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma: Results from Pivotal Study 302. Blood. 2022. doi:https://doi.org/10.1182/blood-2022-166916