ENGAGE-501: Phase II study of entinostat (SNDX-275) in relapsed and refractory hodgkin lymphoma

Connie Lee Batlevi, Yvette Kasamon, Robert G Bociek, Peter Lee, Lia Gore, Amanda Copeland, Rachel Sorensen, Peter Ordentlich, Scott Cruickshank, Lori Kunkel, Daniela Buglio, Francisco Hernandez-Ilizaliturri, Anas Younes

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)968-975
Number of pages8
JournalHaematologica
Volume101
Issue number8
DOIs
StatePublished - Jul 31 2016

Fingerprint

Hodgkin Disease
Appointments and Schedules
entinostat
Hypophosphatemia
Therapeutics
Intention to Treat Analysis
Histone Deacetylase Inhibitors
Pericarditis
Hypokalemia
Pericardial Effusion
Leukopenia
Drug Delivery Systems
Neutropenia
Thrombocytopenia
Disease-Free Survival
Antibody Formation
Disease Progression
Anemia
Protein Isoforms
Stem Cells

ASJC Scopus subject areas

  • Hematology

Cite this

ENGAGE-501 : Phase II study of entinostat (SNDX-275) in relapsed and refractory hodgkin lymphoma. / Batlevi, Connie Lee; Kasamon, Yvette; Bociek, Robert G; Lee, Peter; Gore, Lia; Copeland, Amanda; Sorensen, Rachel; Ordentlich, Peter; Cruickshank, Scott; Kunkel, Lori; Buglio, Daniela; Hernandez-Ilizaliturri, Francisco; Younes, Anas.

In: Haematologica, Vol. 101, No. 8, 31.07.2016, p. 968-975.

Research output: Contribution to journalArticle

Batlevi, CL, Kasamon, Y, Bociek, RG, Lee, P, Gore, L, Copeland, A, Sorensen, R, Ordentlich, P, Cruickshank, S, Kunkel, L, Buglio, D, Hernandez-Ilizaliturri, F & Younes, A 2016, 'ENGAGE-501: Phase II study of entinostat (SNDX-275) in relapsed and refractory hodgkin lymphoma', Haematologica, vol. 101, no. 8, pp. 968-975. https://doi.org/10.3324/haematol.2016.142406
Batlevi, Connie Lee ; Kasamon, Yvette ; Bociek, Robert G ; Lee, Peter ; Gore, Lia ; Copeland, Amanda ; Sorensen, Rachel ; Ordentlich, Peter ; Cruickshank, Scott ; Kunkel, Lori ; Buglio, Daniela ; Hernandez-Ilizaliturri, Francisco ; Younes, Anas. / ENGAGE-501 : Phase II study of entinostat (SNDX-275) in relapsed and refractory hodgkin lymphoma. In: Haematologica. 2016 ; Vol. 101, No. 8. pp. 968-975.
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