Supplemental Figure 1 from Cytogenetic and Molecular Associations with Outcomes in Higher-Risk Myelodysplastic Syndromes Treated with Hypomethylating Agents plus Venetoclax

Bazinet, Alexandre; Desikan, Sai Prasad; Li, Ziyi; Rodriguez-Sevilla, Juan Jose; Venugopal, Sangeetha; Urrutia, Samuel; Montalban-Bravo, Guillermo; Sasaki, Koji; Chien, Kelly S.; Hammond, Danielle; Kanagal-Shamanna, Rashmi; Ganan-Gomez, Irene; Kadia, Tapan M.; Borthakur, Gautam; DiNardo, Courtney D.; Daver, Naval G.; Jabbour, Elias J.; Ravandi, Farhad; Kantarjian, Hagop; Garcia-Manero, Guillermo

doi:10.1158/1078-0432.25515469.v1

Supplemental Figure 1 from Cytogenetic and Molecular Associations with Outcomes in Higher-Risk Myelodysplastic Syndromes Treated with Hypomethylating Agents plus Venetoclax

journal contribution

posted on 2024-04-01, 07:20 authored by Alexandre Bazinet, Sai Prasad Desikan, Ziyi Li, Juan Jose Rodriguez-Sevilla, Sangeetha Venugopal, Samuel Urrutia, Guillermo Montalban-Bravo, Koji Sasaki, Kelly S. Chien, Danielle Hammond, Rashmi Kanagal-Shamanna, Irene Ganan-Gomez, Tapan M. Kadia, Gautam Borthakur, Courtney D. DiNardo, Naval G. Daver, Elias J. Jabbour, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero

Supplemental Figure 1: Overall survival and event-free survival in HMA-naïve patients by response.

Funding

University of Texas MD Anderson Cancer Center (MD Anderson)

MDS/AML Moonshot

History

ARTICLE ABSTRACT

Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood. We pooled patient data from 3 prospective trials evaluating HMA–venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan–Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations between clinical, cytogenetic, and molecular factors and outcomes. A total of 80 patients (52 HMA-naïve, 28 HMA-failure) were included. ORR was 90% in HMA-naïve and 57% in HMA-failure. Median OS was 28.2 and 8.3 months in HMA-naïve and HMA-failure, respectively. Median EFS was 17.9 and 5.5 months in HMA-naïve and HMA-failure, respectively. In addition, 24/52 (46%) of the HMA-naïve and 3/28 (11%) of the HMA-failure patients proceeded to allogeneic stem cell transplantation (SCT). Factors associated with inferior outcomes were prior HMA failure, complex cytogenetics, trisomy 8, TP53 mutations, and RAS pathway mutations. Mutations in RNA splicing, DNA methylation, and ASXL1 appeared favorable. Blast percentage was not predictive of outcomes. Knowledge of cytogenetic and molecular alterations may help identify which patients with HR-MDS benefit the most from venetoclax.