Denileukin diftitox-cxdl receives U.S. FDA approval for adult patients with R/R cutaneous T-cell lymphoma

On August 8, 2024, it was announced that the U.S. Food and Drug Administration (FDA) had granted approval to denileukin diftitox-cxdl, an IL-2-based immunotherapy, for the treatment of adult patients with relapsed/refractory (R/R) stage I–III cutaneous T-cell lymphoma (CTCL) after ≥1 prior systemic therapy. This approval was based on positive results from the phase III 302 trial (NCT01871727).¹

The 302 trial¹

The 302 trial is a multicenter, open-label, phase III study investigating the safety and efficacy of denileukin diftitox-cxdl in patients with R/R stage I–III CTCL. Among the evaluable patients with CTCL (n = 69):

• Overall response rate was 36.2%
• Complete response rate was 8.7%
• Durable and rapid responses were observed:

• Median time to response was 1.41 months
• Duration of response was ≥6 months for 52.0% of the patients
• 84.4% of skin evaluable patients had a decrease in skin tumor burden and 12.5% showed a complete clearing of skin disease

The most commonly reported adverse reactions in ≥20% of patients were laboratory abnormalities (increased transaminases, albumin decreased), nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome.

Denileukin diftitox-cxdl comes with a boxed warning for capillary leak syndrome, including life-threatening or fatal reactions.