Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome.
BACKGROUND
Quisinostat is a hydroxamate, second-generation, orally available pan-histone deacetylase inhibitor.


OBJECTIVES
To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL).


METHODS
Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers.


RESULTS
Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia.


CONCLUSIONS
Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.