Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study

• Published in: Leukemia & lymphoma Vol. 60; no. 3; pp. 675 - 684
• Main Authors: Walewski, Jan, Paszkiewicz-Kozik, Ewa, Borsaru, Gabriela, Hellmann, Andrzej, Janikova, Andrea, Warszewska, Agnieszka, Mais, Anna, Ammendola, Astrid, Herz, Thomas, Krauss, Babett, Henning, Stefan W.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 23.02.2019
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Biomarkers; Drug Resistance, Neoplasm; epigenetics; Female; histone deacetylase; Histone Deacetylase Inhibitors - administration & dosage; Histone Deacetylase Inhibitors - adverse effects; Histone Deacetylase Inhibitors - pharmacokinetics; Histone Deacetylase Inhibitors - therapeutic use; Hodgkin Disease - diagnosis; Hodgkin Disease - drug therapy; Hodgkin Disease - etiology; Hodgkin Disease - mortality; Hodgkin lymphoma; Humans; Hydroxamic Acids - administration & dosage; Hydroxamic Acids - adverse effects; Hydroxamic Acids - pharmacokinetics; Hydroxamic Acids - therapeutic use; Kaplan-Meier Estimate; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Recurrence; Resminostat; Retreatment; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Sulfonamides - therapeutic use; Treatment Outcome; Young Adult; histone deacetylase; epigenetics; Hodgkin lymphoma; Resminostat
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2018.1492122

This open-label, single-arm phase II study examined efficacy, safety, pharmacokinetics, and biomarkers of histone deacetylase (HDAC) inhibitor resminostat in patients with relapsed or refractory Hodgkin lymphoma. Thirty-seven heavily pretreated patients received 600 (19 patients) or 800 mg (18 patients) oral resminostat daily for the initial 5 days of 14-day treatment cycles. Objective response rate (ORR) (primary) was 34% reaching disease control in 54% patients. Most patients (69%) showed reduced tumor size and reduced [ 18 F]-FDG uptake in target lesions (71%). Median progression-free survival (PFS) was 2.3 months (95%CI [1.3; 3.3]) and median overall survival (OS) was 12.5 months (95%CI [9.6; 18.6]). Patients who responded or stabilized under resminostat had a 10-month longer OS than patients who progressed. Efficacy assessment, pharmacodynamics, and exploratory biomarker results followed plasma levels, showed target engagement and epigenetic modulations. Common drug-related adverse events (AEs) were nausea, vomiting, anemia, thrombocytopenia, and fatigue, mainly grade 1 or 2.