Linperlisib plus chidamide shows therapeutic potential in cutaneous T-cell lymphoma

Combination treatment with the PI3Kδ inhibitor linperlisib plus the histone deacetylase inhibitor chidamide has demonstrated promising clinical activity in relapsed or refractory cutaneous T-cell lymphoma (CTCL) in a phase I study.

The study included 22 patients (median age 44 years, 45.5 percent female), of which 19 (86.4 percent) had mycosis fungoides and three (13.6 percent) had Sézary syndrome. All patients had histologically confirmed advanced CTCL, an ECOG performance status of 0–2, and received a median of three prior systemic therapies.

The patients were treated with oral linperlisib (administered once daily in escalating doses of 40, 60, or 80 mg) plus chidamide (20 mg, administered twice weekly). Treatment continued until disease progression, unacceptable toxic effects, or withdrawal.

The 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.

No dose-limiting toxic effects were seen over a median follow-up of 8.9 months, with 80 mg being the recommended phase II dose for linperlisib. Commonly reported treatment-related adverse events (AEs) were nausea (36.4 percent), pruritus (31.8 percent), and skin rash (27.3 percent). Most of these events were grade 1 to 2. Five patients experienced grade 3 AEs (22.7 percent), and none had grade 4 to 5 AEs.

The objective response rate was 59.1 percent (95 percent confidence interval, 38.7–76.7), which comprised two complete responses and 11 partial responses. The disease control rate was 86.4 percent, and the median progression-free survival was 5.4 months.