Linperlisib Plus Chidamide in Relapsed or Refractory Cutaneous T-Cell Lymphoma

作者：Zhiyu Pang, Yupeng Wang, Zhaorui Liu, Shan Zhang, Chong Wei, Zhuofan Xu, Ziqian Wang, Hongyun Chen, Jie Liu, Wei Zhang · 发表于：JAMA Dermatology · 年份：2025 · DOI：10.1001/jamadermatol.2025.1926 · 被引用次数：8 · 研究领域：Cutaneous lymphoproliferative disorders research、Histone Deacetylase Inhibitors Research、Lymphoma Diagnosis and Treatment

Importance: Patients with relapsed or refractory (r/r) cutaneous T-cell lymphoma (CTCL) have limited treatment options. Combining agents that target complementary oncogenic pathways may enhance efficacy while maintaining tolerability. Objective: To evaluate the safety and efficacy of linperlisib, a PI3Kδ inhibitor, combined with chidamide, a histone deacetylase inhibitor, in patients with r/r CTCL. Design, Setting, and Participants: This prospective, single-arm, phase 1 nonrandomized clinical trial with a 3 + 3 dose-escalation phase followed by dose expansion was conducted at a tertiary referral hospital in China from May 1, 2023, to March 6, 2025, with a median follow-up of 8.9 months (range, 1-21 months). It included patients with histologically confirmed advanced CTCL. All had an Eastern Cooperative Oncology Group performance status of 0 to 2 and received a median (range) of 3 (1-7) prior systemic therapies. Patients were enrolled consecutively based on eligibility. Interventions: Oral linperlisib administered once daily in escalating doses (40 mg, 60 mg, or 80 mg) plus chidamide, 20 mg, twice weekly. Treatment continued until progression, unacceptable toxic effects, or withdrawal. Main Outcomes and Measures: Primary outcomes were dose-limiting toxic effects, maximum tolerated dose, and objective response rate. Secondary outcomes included safety, progression-free survival, and disease control rate. Results: Of 22 patients (19 [86.4%] with mycosis fungoides, 3 [13.6%] with ...