2026 ASH®
Annual Meeting & Exposition December 12-15, 2026 ▪ New Orleans, Louisiana

Begin New Search

Paper Details

Abstracts, authors, affiliations, and disclosures.

SESSION

637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster I

Program: Poster Abstract Session
Saturday, December 12, 2026
05:30 p.m. - 07:30 p.m.
MCCNO - Hall F

KEYWORDS

Technology and Procedures, Assays, Molecular Testing, Emerging Technologies, Profiling, Treatment Considerations, Drug Development, Therapy Sequence, Biological Therapies, Antibody Therapy, Transplantation, Immunotherapy, Infusion, Monoclonal Antibody Therapy, Non-Biological Therapies, Chemotherapy, Artificial Intelligence (AI), Deep Learning, Generative AI, Machine Learning, Natural Language Processing, Biological Processes, CHIP, Genomics, Hematopoiesis, Immune Mechanism, Molecular Biology, Clinical Practice (Health Services and Quality), Clinical Guidelines, Quality Improvement, Diseases, Lymphoid Malignancies, Myeloid Malignancies, Acute Myeloid Malignancies, Chronic Myeloid Malignancies, Research, Fundamental Science, AML, Translational Research, MDS, MPN, CMML, Clinical Research, Clinical Trials, Epidemiology, Health Outcomes Research, Patient-Reported Outcomes, Real-World Evidence, Survivorship, Study Population, Human, Adult
PAPER

2096 Selective benefit in higher-risk MDS vs. broad efficacy in AML: Defining HMA+venetoclax clinical benefit using the PRISM score in 5,751 patients- an analysis from the validate database of the international Consortium for MDS (icMDS)

AUTHORS

Maximilian Stahl, MD, Parisa Abedi, MD2, Luca Lanino, MD3, Jan Philipp Bewersdorf, MD4, Tariq Kewan, MD5, Wei Wei, PhD6, Henry Dumke, MD7, Rohan K Achar, MD, MSCR8, Razan Mansour, MD9, tulika rudragupta, MS10, Najla Al Ali, MS11, Amy DeZern, MD, MHS12, Mikkael A. Sekeres, MD13, Geoffrey L. Uy, MD14, Samuel Urrutia, MD, MS15, Hetty Carraway, MD, MBA16, Pinkal Desai, MD, MPH17, Elizabeth A Griffiths, MD18, Eytan M Stein I, MD19, Andrew M Brunner, MD20, Christine M. McMahon, MD21, Rory Shallis I, MD22, Joshua F. Zeidner, MD23, Michael R. Savona, MD24, Namrata Sonia Chandhok I, MD25, Constantine Logothetis, MD26, Aram Bidikian, MD27, Ted Michael Getz, MD28, Gail J Roboz, MD29, Eunice Sue Wang, MD30, Amyah Harris, MS31, Maria Laura Amaya, MD PhD32, Hayley Hawkins, MD33, Somedeb Ball, MD34, Justin Grenet, MD, MPhil35, Zhuoer Xie, MD,MS36, Yazan F. Madanat, MD37, Yasmin Abaza, MD38, Talha Badar, MD39, Jaclynn Campos, PA-C40, Mrinal M. Patnaik, MD, MBBS41, Jaroslaw P. Maciejewski, MD, PhD, FACP42, David Sallman, MD43, Anoop Enjeti, MD FRCP, FRCPA, PhD44, Kamal Al-Rabi, MD45, Khalid Halahleh, MD46, Zaid Abdel Rahman, MD47, Devendra Hiwase I, Consultant Haematologist48, Maria Diez-Campelo, MD, PhD49, David Valcarcel, MD, PhD50, Claudia Haferlach, MD51, Alessandro Baldi, PhD52, Lisa Pleyer, MD53, Ioannis Kotsianidis, MD PhD54, Vassiliki Pappa Sr, MD55, Valeria Santini, MD56, Angela Consagra, MD57, Seishi Ogawa, MD, PhD58, Yasuhito Nannya59, Mina L Xu, MD60, Alexa Siddon, MD61, Benjamin Rolles, MD62, Jessica Maria Stempel, MD, MHS63, Abdulrahman Alhajahjeh, MD64, Alain Mina, MD65, Luis E. Aguirre, MD, MPH66, Nikolai Podoltsev Podoltsev, MD, PhD67, Lourdes Mendez, MD68, Matteo Giovanni Della Porta, MD69, Aref Al-Kali, M.D.70, Rami Komrokji, MD71, Torsten Haferlach, MD, PhD72, Amer M. Zeidan, MD73

AFFILIATIONS

1 Yale School of Medicine, New Haven, Connecticut, United States
2 Yale School of Medicine, New Haven, Connecticut, United States
3 Yale School of Medicine, New Haven, Connecticut, United States
4 Yale School of Medicine, New Haven, Connecticut, United States
5 Yale School of Medicine, New Haven, Connecticut, United States
6 Yale School of Medicine, New Haven, Connecticut, United States
7 Yale School of Medicine, New Haven, Connecticut, United States
8 Yale School of Medicine, New Haven, Connecticut, United States
9 Yale School of Medicine, New Haven, Connecticut, United States, Yale School of Medicine, New Haven, Connecticut, United States
10 Yale School of Medicine, New Haven, Connecticut, United States
11 Moffitt Cancer Center, Tampa, Florida, United States
12 Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, United States
13 Sylvester Comprehensive Cancer Center, Miami, Florida, United States
14 Washington University School of Medicine, Saint Louis, United States
15 Washington University School of Medicine, Saint Louis, United States
16 Taussig Cancer Institute, Cleveland, Ohio, United States
17 Weill Cornell Medicine, New York, New York, United States
18 Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States
19 Memorial Sloan Kettering Cancer Center, New York, New York, United States
20 Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, United States
21 University of Colorado, Aurora, Colorado, United States
22 Department of Malignant Hematology,, Tampa, Florida, United States
23 University of North Carolina, Chapel Hill, North Carolina, United States
24 Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States
25 Sylvester Comprehensive Cancer Center, Baltimore, Maryland, United States
26 Washington University School of Medicine, Saint Louis, United States
27 Yale School of Medicine, New Haven, Connecticut, United States
28 Yale School of Medicine, New Haven, Connecticut, United States
29 Weill Cornell Medicine, New York, New York, United States
30 Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States
31 Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, United States
32 University of Colorado, Aurora, Colorado, United States
33 Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States
34 Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States
35 Weill Cornell Medicine, New York, New York, United States
36 Moffitt Cancer Center, Tampa, Florida, United States
37 Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas, United States
38 Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, United States
39 Division of Hematology-Oncology, Jacksonville, Florida, United States
40 Division of Hematology-Oncology, Jacksonville, Florida, United States
41 Mayo Clinic, Rochester, Minnesota, United States
42 Taussig Cancer Institute, Cleveland, Ohio, United States
43 Moffitt Cancer Center, Tampa, Florida, United States
44 Department of Haematology, Calvary Mater Hospital, New South Wales, Australia
45 King Hussein Cancer Center, Amman, Jordan
46 King Hussein Cancer Center, Amman, Jordan
47 King Hussein Cancer Center, Amman, Jordan
48 Department of Haematology, The Royal Adelaide Hospital, Adelaide, Australia
49 Hematology Department, Institute of Biomedical Research of Salamanca, Salamanca, Spain
50 Hematology Department, Institute of Biomedical Research of Salamanca,, Salamanca, Spain
51 MLL Munich Leukemia Laboratory, Munich, Germany
52 MLL Munich Leukemia Laboratory, Munich, Germany
53 Paracelsus Medical University, Salzburg, Austria
54 Democritus University of Thrace Medical School, Alexandroupolis, Greece
55 National and Kapodistrian University of Athens, Athens, Greece
56 Ospedale San Giovanni di Dio, Florence, Italy
57 Ospedale San Giovanni di Dio, Florence, Italy
58 Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto, Japan
59 Institute of Medical Science, Tokyo, Japan
60 Yale School of Medicine, New Haven, Connecticut, United States
61 Yale School of Medicine, New Haven, Connecticut, United States
62 Yale School of Medicine, New Haven, Connecticut, United States
63 Yale School of Medicine, New Haven, Connecticut, United States
64 Yale School of Medicine, New Haven, Connecticut, United States
65 Yale School of Medicine, New Haven, Connecticut, United States
66 Yale School of Medicine, New Haven, Connecticut, United States
67 Yale School of Medicine, New Haven, Connecticut, United States
68 Yale School of Medicine, New Haven, Connecticut, United States
69 IRCCS Humanitas Research Hospital, Milano, Italy
70 Mayo Clinic, Rochester, Minnesota, United States
71 Moffitt Cancer Center, Tampa, Florida, United States
72 MLL Munich Leukemia Laboratory, Munich, Germany
73 Yale School of Medicine, New Haven, Connecticut, United States

ABSTRACT

Background: The VERONA trial showed that adding venetoclax to azacitidine (HMA+VEN) did not improve overall survival (OS) in higher-risk MDS (HR-MDS) despite higher response rates. Whether this reflects absence of benefit or benefit limited to a subset diluted out in an all-comers cohort remains unclear. The Prognostic Risk Integration for Survival Modeling (PRISM) score was developed for prognostication in AML treated with HMA+VEN, but whether it can identify subsets deriving differential benefit from HMA+VEN over HMA monotherapy in HR-MDS is unknown. We sought to evaluate whether the PRISM score identified pts who are more likely to derive clinical benefit from HMA+VEN across 5,751 pts with HR-MDS and AML in three independent cohorts.

Methods: The icMDS VALIDATE cohort of HR-MDS pts (n=1,828) treated with first-line HMA+VEN or HMA monotherapy was analyzed and results were compared with two separate AML cohorts: VALIDATE-AML (n=812) and Flatiron Health Research Database (n=3,111). Inverse Probability of Treatment Weighting (IPTW) adjusted baseline imbalances between HMA+VEN and HMA treated pts within each cohort. Model discrimination was quantified via Harrell's C-index. Cox models evaluated treatment-by-PRISM interactions to assess whether the OS benefit of HMA+VEN varied across PRISM strata. VALIDATE-MDS received funding from an independent grant by Abbvie which had no role in research design or abstract writing.

Results: In VALIDATE-MDS, 121 pts received HMA+VEN and 1,707 received HMA monotherapy. In HMA+VEN treated pts, IPSS-M was skewed toward very high risk (very high: 56.2%, high: 24.6%, other: 19.2%), while PRISM tiers were more evenly distributed (low: 24.0%, moderate: 37.2%, high: 38.8%). Molecular abnormalities mediating venetoclax resistance were rare in pts with PRISM low vs high risk (TP53: 0% vs 94%; complex karyotype: 6.9% vs. 87%, both p<0.001). Further, venetoclax sensitizing mutations were enriched in low vs high PRISM risk (IDH2: 24% vs 0%; RUNX1: 31% vs 0%, both p<0.001). Pts with high PRISM exhibited deeper cytopenias, including lower hemoglobin (8.3 vs 9.3 g/dL, p=0.006) and platelets (46 vs 99 × 10?/L, p=0.01). In contrast, there was no significant difference in bone marrow blast percentage between pts with low vs high PRISM risk (14% vs 12% p=0.39) and no difference between distribution of blasts <5%/ 5%-9%/ ≥10% (3.4%/21%/76% vs. 13%/23%/64%, p=0.681).

PRISM was prognostic (C-index 0.76 [95% CI 0.70-0.81]); median OS for HMA+VEN pts declined across tiers (not reached vs 26.0 vs 7.6 mo). HMA+VEN-by-PRISM interaction was significant (p<0.001) indicating that the benefit of HMA+VEN over monotherapy varies across the PRISM spectrum. Low PRISM pts derived marked OS benefit with HMA+VEN vs HMA (5 year OS: 60% vs 22%, HR 0.19, p=0.001); no significant benefit was seen in moderate (5 year OS: 15% vs 14%, HR 0.71, p=0.13) or high (5 year OS: 8% vs 8%, HR 0.94, p=0.73) tiers.

While IPSS-M was prognostic, it was not predictive of differential benefit of HMA+VEN vs. HMA (interaction HR 1.09, p=0.356). Overall, 44.6% of pts had discordant risk between IPSS-M and PRISM. Pts with high/very high IPSS-M disease downstaged to low risk per PRISM (19% of pts) achieved longer OS compared to those remaining moderate/high risk per PRISM (5-year OS: 56% vs. 14%; HR 0.23, 95% CI 0.10-0.54, p<0.001).

In both AML cohorts (VALIDATE-AML: 491 HMA+VEN vs 321 HMA treated pts; Flatiron: 1,792 HMA+VEN vs 1,319 HMA treated pts), PRISM demonstrated prognostic value (C-index 0.64 and 0.61, respectively). Unlike in HR-MDS, the treatment-by-PRISM interaction was not significant (VALIDATE-AML p=0.31; Flatiron p=0.074), reflecting broad HMA+VEN survival benefit across all PRISM risk tiers. Per-tier hazard ratios comparing HMA+VEN with HMA confirmed consistent benefit in VALIDATE-AML (Low: HR 0.46, p<0.001; Moderate: HR 0.56, p=0.002; High: HR 0.71, p=0.075) and Flatiron (Low: HR 0.58; Moderate: HR 0.76; High: HR 0.73; all p<0.001).

Conclusions: While HMA+VEN failed to improve OS in unselected patients with HR-MDS, the PRISM score might be able to identify a subgroup of patients in which HMA+VEN could improve OS compared to HMA monotherapy. In contrast, no statistically significant evidence of treatment-effect heterogeneity by PRISM score was observed in either AML cohort. Validation in larger prospective cohorts is required to confirm the PRISM score's utility in identifying HR-MDS subsets benefiting from HMA+VEN over HMA monotherapy.

DISCLOSURES

Maximilian Stahl, MD: Novartis - Honoraria; Curis Oncology - Honoraria; Haymarket Media - Honoraria; Clinical Care Options - Honoraria; Rigel - Consultancy (Includes expert testimony); Takeda Pharmaceuticals - Consultancy (Includes expert testimony); Sierra Oncology - Consultancy (Includes expert testimony); Pharmaessentia - Consultancy (Includes expert testimony); Novartis - Consultancy (Includes expert testimony); Dedham Group - Consultancy (Includes expert testimony); BMS - Consultancy (Includes expert testimony); Servier - Consultancy (Includes expert testimony); GSK - Consultancy (Includes expert testimony); Syndax - Consultancy (Includes expert testimony); Daiichi Sankyo - Consultancy (Includes expert testimony); Kura Oncology - Consultancy (Includes expert testimony); Sobi - Consultancy (Includes expert testimony); Boston Consulting Group - Consultancy (Includes expert testimony); Syndax - Consultancy (Includes expert testimony); Kymera - Consultancy (Includes expert testimony); GLG - Consultancy (Includes expert testimony); Incyte - Consultancy (Includes expert testimony)
Begin New Search