Emerging Therapeutic Strategies in Cutaneous T-Cell Lymphoma: A Comprehensive Review of Clinical Trials - PubMed
18 hours ago
- #Therapeutic strategies
- #Clinical trials
- #Cutaneous T-cell lymphoma
- The review covers clinical trials in cutaneous T-cell lymphoma (CTCL) from 2015 to 2025, focusing on 134 interventional trials after exclusions.
- Trials include antibody and biologic therapies, epigenetic modifiers, signaling pathway inhibitors, immunotherapy, cellular therapies, and skin-directed treatments.
- Notable approvals include denileukin diftitox-cxdl in 2024 for relapsed/refractory CTCL and breakthrough designation for lacutamab in 2025 for Sézary syndrome.
- Lacutamab showed a 43% overall response rate with a median duration of 25.6 months in Sézary syndrome.
- CAR-T therapy, specifically CTX130, achieved a 46% overall response rate in heavily pretreated patients, overcoming T-cell fratricide issues.
- Combination strategies, such as HDAC inhibitors with PI3K inhibitors, achieved 50-60% response rates in refractory cases.
- For early-stage disease, HyBryte photodynamic therapy demonstrated efficacy in the Phase 3 FLASH trial.
- The RESMAIN trial, despite meeting its primary endpoint, failed regulatory approval due to quality-of-life issues from gastrointestinal toxicity.
- Future developments should prioritize patient-reported outcomes, biomarker validation, and combination therapies with non-overlapping toxicities.