Prospective Performance of the IWG-2023 Criteria and IPSS-M in a Phase 2 Trial of Guadecitabine for Higher-Risk MDS or CMML

Authors

Samuel Urrutia
Prithviraj Bose
Yesid Alvarado
Gautam Borthakur
Farhad Ravandi
Naval Daver
Naveen Pemmaraju
Elias Jabbour
Koichi Takahashi
Tapan Kadia
Courtney DiNardo
Steven Kornblau
Rashmi Kanagal-Shamanna
Xuelin Huang
Kristy Bodden
Hagop Kantarjian
Guillermo Garcia-Manero

Publication Date

6-1-2024

Journal

Blood Neoplsasia

DOI

10.1016/j.bneo.2024.100008

PMID

40454402

PMCID

PMC12082099

PubMedCentral® Posted Date

3-29-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had TP53 mut . By the International Working Group 2006 (IWG-2006) criteria, 25% achieved complete remission (CR), 30% marrow CR, and 33% no response (NR). Common grade 3 events were febrile neutropenia (32%) and infection (25%). Mortality rates at 4 and 8 weeks were 0% and 4%, respectively. The median overall survival (mOS) was 16.8 months. Patients who underwent transplantation (21%) had an mOS of 46.6 months. We then reanalyzed this data set using IPSS-Molecular (IPSS-M) and IWG-2023 response criteria. By IPSS-M, 60% of patients were classified as very high and 27% as high risk. By IWG-2023, overall response rate was 52%, with 30% CR, 14% CR with limited count recovery, and 42% NR. IPSS-M provided adequate risk stratification at enrollment. Patients classified as marrow CR had widely different outcomes when reclassified by IWG-2023. In conclusion, SGI-110 was active in high-risk MDS, but survival is unlikely to be superior to current hypomethylating agents. The study is registered at www.ClinicalTrials.gov as #NCT02131597.

Published Open-Access

yes

Recommended Citation

Urrutia, Samuel; Bose, Prithviraj; Alvarado, Yesid; et al., "Prospective Performance of the IWG-2023 Criteria and IPSS-M in a Phase 2 Trial of Guadecitabine for Higher-Risk MDS or CMML" (2024). Faculty, Staff and Student Publications. 4416.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4416