Anaysis: Linperlisib and Chidamide Safe, Effective in Advanced CTCL

07/09/2025

Key Takeaways:

  • New research shows linperlisib plus chidamide showed a 59.1% objective response rate and 86.4% disease control rate in relapsed/refractory cutaneous T-cell lymphoma.

  • The combination had a manageable safety profile and no dose-limiting toxicities, supporting further evaluation.

An investigational combination of linperlisib and chidamide demonstrated clinical activity in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL), according to results from a phase 1 trial.

The single-arm, nonrandomized study looked at PI3Kδ inhibitor linperlisib in escalating doses (40 mg, 60 mg, 80 mg daily) alongside twice-weekly chidamide (20 mg) in 22 patients with histologically confirmed advanced CTCL. Almost 87% of patients had mycosis fungoides (median age, 44 years). All participants previously received a median of three systemic therapies. The endpoints of interest included dose-limiting toxicity, maximum tolerated dose (MTD), and objective response rate (ORR). 

The researchers reported an ORR of 59.1% (13 of 22; two complete and 11 partial responses) and a disease control rate of 86.4%. Median progression-free survival was 5.4 months. The most commonly reported treatment-related adverse events were included nausea, pruritus, and rash. 22.7% of patients experienced grade 3 events.

"This nonrandomized clinical trial found that plus chidamide showed a manageable safety profile and promising activity in r/r CTCL," the authors wrote. "This all-oral combination may represent a new therapeutic option for advanced CTCL, particularly in mycosis fungoides.”

Source: Pang Z, et al. JAMA Dermatology. 2025. doi:10.1001/jamadermatol.2025.1926

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