NCCN Guidelines Add Denileukin Diftitox for CTCL Treatment

The National Comprehensive Cancer Network (NCCN) has added denileukin diftitox-cxdl (Lymphir; ​​E7777) to its clinical practice guidelines in oncology, based on an NCCN category 2A recommendation that indicates the agent is an adequate option for the treatment of patients with cutaneous T-cell lymphoma (CTCL).¹

Denileukin diftitox is a novel immunotherapy approved by the FDA in August 2024 for the treatment of relapsed/refractory CTCL after at least 1 previous systemic therapy. Findings from the pivotal phase 3 trial titled Study 302 (NCT01871727) supported its approval.

In the study, the primary efficacy population consisted of 69 patients with stage I to III CTCL who were treated with the agent at a dose of 9 mcg/kg/day with a median of 6 cycles (range, 1-42) of treatment.² Findings showed that the overall response rate (ORR) by independent review committee was 36.2% (95% CI, 25.0%-48.7%), with 8.7% of patients reaching a complete response (CR). The ORR by investigator assessment was 42.3% (range, 30.6%-54.6%) with 8.5% reaching a CR. Further, the duration of response was at least 6 months for 52% of responders (n = 13), at least 12 months for 20% (n = 5), and approximately 70% of responders had a response within 1 to 2 cycles of treatment, with a median time to response of 1.41 months.

"The inclusion of [denileukin diftitox] in the NCCN guidelines is a testament to the clinical evidence supporting this therapy, and further supports healthcare professionals in considering [denileukin diftitox] as part of the recommended treatment protocols for CTCL. We are grateful to the NCCN board for its recognition of [denileukin diftitox], paving the way for expanded access to this important treatment option," said Leonard Mazur, chief executive officer of Citius Pharma and Citius Oncology, in a press release.¹

Denileukin diftitox is an interleukin-2 (IL-2)-based immunotherapy indicated for use in patients with stage I to III CTCL following at least 1 prior systemic therapy. In 2021, the agent was granted regulatory approval in Japan for the treatment of CTCL and peripheral T-cell lymphoma. In the same year, Citius Oncology acquired an exclusive license with rights to develop and commercialize denileukin diftitox in all markets, excluding Japan and specific parts of Asia.¹

Notably, denileukin diftitox marks the only agent in CTCL to target the IL-2 receptor found on malignant T-cells and Tregs.

"NCCN guidelines are widely regarded as the gold standard for clinical decision-making in oncology and hematology, influencing treatment practices and payor reimbursement in the U.S. We believe that [denileukin diftitox] has the potential to improve CTCL patient outcomes and expect its addition to the NCCN guidelines may aid adoption and ease reimbursement, particularly for the anticipated patients that qualify for Center for Medicare and Medicaid coverage," added Mazur in the press release.

REFERENCES:

1. Citius Pharmaceuticals, Inc. and Citius Oncology, Inc. announce LYMPHIR™ (denileukin diftitox-cxdl) added to national comprehensive cancer network (NCCN) clinical practice guidelines in oncology. News release. Citius Pharmaceuticals, Inc. September 5, 2024. Accessed September 9, 2024. https://tinyurl.com/2s4n8hwy

2. Foss F, Kim Y, Prince MM, 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;140(Suppl 1): 1491–1492. doi:10.1182/blood-2022-166916