ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma.

Abstract

Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel therapies is warranted to improve patient outcomes. In this phase II study, patients with relapsed or refractory Hodgkin lymphoma were treated with entinostat, an isoform selective histone deacetylase inhibitor. Forty-nine patients were enrolled: 33 patients on Schedule A (10 or 15 mg oral entinostat once every other week); 16 patients on Schedule B (15 mg oral entinostat once weekly in 3 of 4 weeks). Patients received a median of 3 prior treatments (range 1-10), with 80% of the patients receiving a prior stem cell transplant and 8% of patients receiving prior brentuximab vedotin. In the intention-to-treat analysis, the overall response rate was 12% while the disease control rate (complete response, partial response, and stable disease beyond 6 months) was 24%. Seven patients did not complete the first cycle due to progression of disease. Tumor reduction was observed in 24 of 38 (58%) evaluable patients. Median progression-free survival and overall survival was 5.5 and 25.1 months, respectively. The most frequent grade 3 or 4 adverse events were thrombocytopenia (63%), anemia (47%), neutropenia (41%), leukopenia (10%), hypokalemia (8%), and hypophosphatemia (6%). Twenty-five (51%) patients required dose reductions or delays. Pericarditis/pericardial effusion occurred in one patient after 12 cycles of therapy. Future studies are warranted to identify predictive biomarkers for treatment response and to develop mechanism-based combination strategies. (clinicaltrials.gov identifier: 00866333).

• Authors: Connie Lee Batlevi, Yvette Kasamon, R Gregory Bociek, Peter Lee, Lia Gore, Amanda Copeland, Rachel Sorensen, Peter Ordentlich, Scott Cruickshank, Lori Kunkel, Daniela Buglio, Francisco Hernandez-Ilizaliturri, Anas Younes
• Journal: Haematologica (Haematologica) Vol. 101 Issue 8 Pg. 968-75 (08 2016) ISSN: 1592-8721 [Electronic] Italy
• PMID: 27151994 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Antineoplastic Agents
• Benzamides
• Cytokines
• Histone Deacetylase Inhibitors
• Pyridines
• entinostat

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Benzamides (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Combined Modality Therapy
• Cytokines (blood)
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Histone Deacetylase Inhibitors (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Hodgkin Disease (diagnosis, drug therapy, mortality)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multimodal Imaging
• Pyridines (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Recurrence
• Retreatment
• Treatment Outcome
• Young Adult