A phase II study of addition of pracinostat to a hypomethylating agent in patients with myelodysplastic syndromes who have not responded to previous hypomethylating agent therapy

Fevzi F. Yalniz, Jesus G. Berdeja, Michael B. Maris, Roger M. Lyons, James A. Reeves, James H. Essell, Prapti Patel, Mikkael Sekeres, Amanda Hughes, Silvia Mappa, Guillermo Garcia-Manero

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Hypomethylating agents (HMAs) are standard of care for higher-risk myelodysplastic syndromes (MDS). However, less than half of patients achieve objective responses and most eventually lose their response. Pracinostat is a pan-histone deacetylase inhibitor with demonstrated activity in advanced myeloid malignancies. This phase II study explored the benefit of adding pracinostat to HMAs in MDS patients who did not respond to single-agent HMA treatment. The goal was to estimate the clinical improvement rate [complete remission (CR), marrow CR, partial response (PR) and haematological improvement]. Group 1 included patients with primary/secondary HMA failures; Group 2 included those who did not achieve response but had stable disease (SD) after single-agent HMAs. Forty-five patients (39 Group 1, 6 Group 2) received a median of 3 cycles. Among all patients, 1 (2%) had CR, 7 (16%) had marrow CR and 18 (40%) had SD; disease progression occurred in 3 (7%). Median overall survival was 5·7/5·6 months for Group 1/2. Grade ≥3 adverse events occurred in 38 patients (84%) leading to treatment discontinuation in 12 (33%). Adding pracinostat to HMAs did not improve outcomes in patients previously treated with HMAs. Frequent dose modifications/early discontinuation resulted in suboptimal drug exposure. A reduced pracinostat dose may improve tolerability and efficacy.

Original languageEnglish (US)
Pages (from-to)404-412
Number of pages9
JournalBritish Journal of Haematology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2020

Keywords

  • HDAC inhibitor
  • azacitidine
  • hypomethylating drugs
  • myelodysplastic syndromes
  • pracinostat

ASJC Scopus subject areas

  • Hematology

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    Yalniz, F. F., Berdeja, J. G., Maris, M. B., Lyons, R. M., Reeves, J. A., Essell, J. H., Patel, P., Sekeres, M., Hughes, A., Mappa, S., & Garcia-Manero, G. (2020). A phase II study of addition of pracinostat to a hypomethylating agent in patients with myelodysplastic syndromes who have not responded to previous hypomethylating agent therapy. British Journal of Haematology, 188(3), 404-412. https://doi.org/10.1111/bjh.16173