In the study, eight of 33 patients with advanced, refractory cutaneous T-cell lymphoma (CTCL) experienced partial responses, the primary endpoint of the study.
The most common side effects seen in the study were fatigue (85%), diarrhea (58%), nausea (61%), change in taste (58%), dry mouth (42%), decreased appetite (21%), and low platelet count (30%).
“In this study, SAHA demonstrated encouraging improvements in the overall condition of patients with advanced, refractory, and heavily pretreated CTCL as assessed by their physician’s global assessments,” said Dr Madeleine Duvic, professor of medicine and deputy chairman of the department of dermatology at MD Anderson Cancer Center and lead investigator of the study. “SAHA was shown to reduce the tumor burden and improve pruritus in CTCL patients, especially those with erythroderma and Sezary syndrome.”
Suberoylanilide hydroxamic acid (SAHA) is believed to inhibit the enzyme histone deacetylase (HDAC). Histones are structural proteins, around which DNA coils, that may play an important role in the regulation of gene expression. Increased levels of HDAC, which are present in tumor cells, trigger histones to tightly package DNA and limit the transcription of tumor suppressor genes. By changing the balance between acetylated and deacetylated proteins, SAHA causes cell cycle arrest, cell differentiation, and apoptosis.
SAHA was granted fast-track designation and orphan drug designation for CTCL by the FDA. Merck is conducting a confirmatory phase IIb trial with SAHA in CTCL patients and is pursuing clinical studies with SAHA in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma.