Impact of Response to Hypomethylating Agent-Based Therapy on Survival Outcomes in the Context of Baseline Clinical-Molecular Risk and Transplant Status in Patients with Myelodysplastic Syndromes/Neoplasms (MDS): An Analysis from the International Consortium for MDS (icMDS) Validate Database

Rolles, Benjamin

Oral and Poster Abstracts
Oral
637. Myelodysplastic Syndromes: Clinical and Epidemiological: Treatment and Prognostication of MDS

Research, Adult, MDS, Health outcomes research, Clinical Research, Chronic Myeloid Malignancies, Diseases, Real-world evidence, Myeloid Malignancies, Human, Study Population

Benjamin Rolles, MD^1,2, Jan Philipp Bewersdorf, MD^3,4, Tariq Kewan, MD⁵, Ondrej Blaha, PhD⁶^*, Jessica M. Stempel, MD³, Luca Lanino, MD⁷, Najla H. Al Ali, Ms⁸^*, Amy E. DeZern, MD⁹, Mikkael A. Sekeres, MD¹⁰, Geoffrey L. Uy, MD¹¹, Hetty E. Carraway, MD, MBA¹², Pinkal Desai¹³, Elizabeth A. Griffiths, MD¹⁴, Eytan M. Stein, MD¹⁵, Andrew M. Brunner, MD¹⁶, Christine M. McMahon, MD¹⁷, Rory M. Shallis, MD³, Joshua F. Zeidner, MD¹⁸, Michael R. Savona, MD¹⁹, Stacey M. Frumm, MD²⁰, Shougat Barua²¹^*, Namrata S. Chandhok, MD¹⁰, Constantine Logothetis, MD¹¹, Aram Bidikian, MD³, Ted M. Getz, MD³, Gail J. Roboz, MD²², Eunice S. Wang, MD²³, Amyah C. Harris¹⁶^*, Maria L Amaya, MD, PhD¹⁷, Hayley Hawkins²⁴^*, Somedeb Ball, MD¹⁹, Justin Grenet, MD, MPhil¹³, Zhuoer Xie, MD, MS²⁵, Yazan F Madanat, MD²⁶, Yasmin Abaza, MD²⁷, Talha Badar, MD²⁸, Torsten Haferlach, MD²⁹, Jaroslaw Maciejewski³⁰, David Sallman, MD³¹, Anoop K Enjeti, MBBS, FRCPA, MD, MRCP³², Kamal Al-Rabi, MD³³^*, Khalid Halahleh, MD³³^*, Devendra Hiwase, MD, MBBS, PhD, FRACP, FRCPA³⁴, Maria Diez-Campelo, MD, PhD³⁵^*, David Valcarcel, MD, PhD³⁶, Claudia Haferlach, MD²⁹, Lisa Pleyer, MD³⁷^*, Ioannis Kotsianidis, PhD³⁸, Vassiliki Pappa, MD³⁹, Valeria Santini, MD⁴⁰, Angela Consagra, MD⁴⁰^*, Aref Al-Kali, MD⁴¹, Seishi Ogawa, MD, PhD⁴², Yasuhito Nannya, MD, PhD⁴², Matteo Giovanni Della Porta, MD⁴³^*, Rami S. Komrokji, MD²⁵, Amer M. Zeidan, MBBS, MHS³ and Maximilian Stahl, MD²

¹Division of Hematology, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA
²Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
³Department of Internal Medicine, Section of Hematology, Yale University, New Haven
⁴Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY
⁵Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
⁶School of Public Health, Yale Center for Analytical Sciences, Yale University, New Haven
⁷IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
⁸Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa
⁹Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore
¹⁰Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami
¹¹Washington University School of Medicine, Saint Louis
¹²Department of Hematology and Medical Oncology, Taussig Cancer Institute, Leukemia Program, Cleveland Clinic, Cleveland, OH
¹³Weill Cornell Medicine, New York City
¹⁴Roswell Park Comprehensive Cancer Center, Buffalo, NY
¹⁵Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York City
¹⁶Division of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston
¹⁷University of Colorado, Aurora
¹⁸Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill
¹⁹Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville
²⁰Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston
²¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston
²²Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY
²³Roswell Park Comprehensive Cancer Center, Buffalo
²⁴Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
²⁵Department of Malignant Hematology, H Lee Moffitt Cancer Center, Tampa, FL
²⁶Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas
²⁷Northwestern University, Chicago
²⁸Division of Hematology-Oncology, Mayo Clinic, Jacksonville
²⁹MLL Munich Leukemia Laboratory, Munich, Germany
³⁰Department of Hematology and Medical Oncology, Taussig Cancer Institute, Leukemia Program, Cleveland Clinic, Cleveland
³¹Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa
³²Department of Haematology, Calvary Mater Hospital, Newcastle, Australia
³³King Hussein Cancer Center, Amman, Jordan
³⁴Department of Haematology, The Royal Adelaide Hospital, Adelaide, SA, Australia
³⁵Hematology Department, Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, Salamanca, Spain
³⁶Department of Hematology and Oncology, University Hospital Vall d'Hebron, Barcelona, Spain
³⁷3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
³⁸Department of Hematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
³⁹Hematology Division, Second Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
⁴⁰MDS Unit, Hematology, AOU Careggi ‐ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
⁴¹Mayo Clinic, Rochester
⁴²Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
⁴³IRCCS Humanitas Clinical and Research Center, Rozzano, Italy

Introduction: Response assessment is used to evaluate effectiveness of hypomethylating agent (HMA)-based therapy in myelodysplastic syndromes/neoplasms (MDS) in clinical practice and trials. Recently, the clinical response criteria (IWG 2023) and the clinical-molecular risk assessment (IPSS-M) in MDS were published. However, it remains unknown whether the IWG 2023 response criteria have an independent impact on overall survival (OS) when adjusting for baseline IPSS-M risk. Additionally, the association of IWG 2023 response criteria with OS in patients (pts) undergoing allogeneic stem cell transplantation (allo-HCT) versus those who do not is unknown. Lastly, it is unclear if optimal time-to-transplant impacts OS in MDS pts who achieve a IWG 2023 defined remission with HMA therapy. We examined these questions in a large population of MDS pts within the multi-institutional international consortium for MDS (icMDS) VALIDATE database.

Methods: High-risk MDS pts with IPSS ≥1.5 or IPSS-R >3.5 treated with HMA-based therapy were included in the study. Baseline IPSS-M risk was stratified into very low/low/moderate low (VL+L+ML), moderate-high/high (MH+H), and very high (VH). Response to treatment was evaluated using the IWG 2023 criteria and grouped into: composite complete response (cCR) and no cCR. cCR included: complete response (CR), CR equivalent (CRequ), CR bilineage (CRbi), CR unilineage (CRuni), and CR with partial hematologic recovery (CRh). We analyzed the differential impact of achieving cCR on HMA-based therapy prior to transplant on OS in pts who either did or did not undergo allo-HCT, while adjusting for their baseline IPSS-M risk in Cox regression analysis. Optimal time-to-transplant was determined based on age and IPSS-M category as described by Tentori et al. (JCO 2024). Pts proceeding to allo-HCT were stratified on whether they underwent transplant within the optimal time-to-transplant timeframe after MDS diagnosis or not. VALIDATE protocol was exempted, acknowledged, or approved by all centers’ IRBs. VALIDATE is supported by an independent grant from AbbVie.

Results: We analyzed 762 MDS pts. The median age at MDS diagnosis was 68 years (range: 19-95 years) and 64% of pts were male. Distribution of the baseline IPSS-M risk was: VL+L+ML in 110 (14%) pts, MH+H in 347 (46%) pts, VH in 305 (40%) pts. Pts received azacitidine monotherapy, decitabine monotherapy, and HMA-based combination therapy (e.g. HMA + venetoclax) in 52%, 21%, and 28% of cases, respectively. A total of 282/762 (37%) pts achieved cCR as their best response to HMA-based therapy. The median OS for all pts was 18.7 months (95% CI: 16.6-21.3 months). Pts who did not undergo allo-HCT (n=436, 57%) had an improved median OS if they achieved cCR when compared to pts in the no cCR group in all IPSS-M risk groups (VL+L+ML: 23.5 months vs. 10.7 months; MH+H: 20.8 months vs. 11.6 months; VH: 13.8 months vs. 7.5 months). Cox analysis demonstrated an independent effect of cCR on OS in these pts when adjusted for baseline IPSS-M risk (cCR vs. no cCR: HR 0.60, 95% CI 0.48-0.76, p<0.001). In contrast, in pts who subsequently received an allo-HCT (n=326, 43%), achieving cCR with HMA prior to allo-HCT did not provide an additional OS benefit, when adjusted for baseline IPSS-M risk (cCR vs. no cCR: HR 1.00, 95% CI 0.73-1.38, p=0.986). The median time-to-transplant was 6.7 months and 34% of transplanted MDS pts received their allo-HCT during the optimal timeframe. Among pts who achieved cCR with HMA-based therapy prior to allo-HCT, optimal time-to-transplant was associated with significantly improved OS (optimal vs. non-optimal timing: HR 0.55; p=0.033).

Conclusion: Baseline IPSS-M risk and allo-HCT had an independent impact on OS, while IWG 2023 defined cCR had an independent effect on OS only in non-transplanted MDS pts. While this retrospective analysis occurred at large academic centers with specific expertise in the management of MDS, our data may have an impact on clinical practice: (i) failure to achieve cCR on HMA therapy prior to transplant should not impact the decision to proceed to allo-HCT, (ii) upfront allo-HCT without prior HMA therapy might also be an option if the clinical situation and availability of donors allow, and (iii) allo-HCT should ideally be performed during the timeframe that is considered optimal as defined by pt age and baseline IPSS-M.

Disclosures: Stempel: Sobi: Other: Advisory Board Participation. DeZern: Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; servier: Membership on an entity's Board of Directors or advisory committees; Keros: Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; geron: Other: dsmb; Appellis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibbs: Membership on an entity's Board of Directors or advisory committees. Sekeres: Schroedinger: Membership on an entity's Board of Directors or advisory committees; Kurome: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. Carraway: Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Stemline: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Desai: Kura Oncology: Consultancy, Other: Research Support; BMS: Consultancy, Other: Research Support; Servier: Consultancy; Rigel: Consultancy; Janssen: Other: Research Support. Griffiths: Servier: Consultancy; Partner Therapeutics: Consultancy; MDS International Foundation: Honoraria; AAMDS: Honoraria; Genentech: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Blueprint Medicines: Research Funding; Celldex Pharmaceuticals: Research Funding; MJH Health: Honoraria; Alexion Pharmaceuticals/ AstraZeneca Rare Disease: Consultancy, Research Funding; Picnic Health: Consultancy; CTI Biopharma: Consultancy; NextCure: Research Funding; MediCom Worldwide: Honoraria; MedscapeLive: Honoraria; Physicians Educational Resource: Honoraria; Abbvie: Consultancy; Apellis Pharmaceuticals: Consultancy, Research Funding; Takeda Oncology: Consultancy; Astex Pharmaceuticals/Taiho Oncology/Otsuka: Consultancy, Research Funding; Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; ASH: Honoraria. Stein: AstraZeneca: Consultancy, Other: consulting fees; Genentech: Consultancy, Other: consulting fees; Daiichi Sankyo, Inc.: Consultancy, Other: consulting fees; Servier: Consultancy, Other: consulting fees; Abbvie: Consultancy, Other: consulting fees; Jazz Pharmaceuticals: Consultancy, Other: consulting fees; Astellas Pharmaceuticals: Consultancy, Other: consulting fees; Gilead: Consultancy, Other: consulting fees; Agios Pharmaceuticals: Consultancy, Other: consulting fees; Celgene: Consultancy, Other: consulting fees. Brunner: Servier: Consultancy; AstraZeneca: Research Funding; Geron: Consultancy; Takeda Oncology: Consultancy, Research Funding; Rigel Pharmaceuticals: Consultancy; Novartis: Consultancy, Research Funding; Lava Therapeutics: Consultancy; Keros Therapeutics: Consultancy; i-Mab Biopharma: Consultancy; BMS: Consultancy, Research Funding; Agios: Consultancy. McMahon: Syros Pharmaceuticals: Research Funding; Syndax Pharmaceuticals, Inc.: Research Funding; Kura Oncology: Membership on an entity's Board of Directors or advisory committees. Shallis: Rigel: Consultancy, Honoraria; Kura Oncology: Consultancy, Honoraria; Gilead Sciences, Inc: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Other: Steering Commitee. Zeidner: Sumitomo Pharma: Consultancy, Research Funding; Stemline: Research Funding; Shattuck Labs: Consultancy, Research Funding; Servier: Consultancy; Sellas Life Sciences: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Newave: Research Funding; Merck: Research Funding; Loxo: Research Funding; Jazz: Research Funding; Gilead: Consultancy, Research Funding; Genmab: Consultancy; Foghorn: Consultancy; Faron: Research Funding; Daiichi Sankyo: Consultancy; AstraZeneca: Research Funding; Astex: Research Funding; Arog: Research Funding; Akeso Biopharma: Research Funding; AbbVie: Consultancy, Research Funding; Syndax: Consultancy; Takeda: Research Funding; Zentalis: Research Funding. Savona: AbbVie; Bristol Myers Squibb; CTI BioPharma Corp.; Geron; Karyopharm; Novartis Pharmaceuticals Corporation; Ryvu Therapeutics; and Sierra Oncology, Inc.: Consultancy; ALX Oncology Inc.; Astex Pharmaceuticals; Incyte Corporation; and Takeda Pharmaceutical Company Limited.: Research Funding; Empath Biosciences; Karyopharm and Ryvu Therapeutics: Current holder of stock options in a privately-held company; Astex Pharmaceuticals for travel grant.: Other: Financial or Material Support. Roboz: Janssen: Research Funding; OncoPrecision: Current holder of stock options in a privately-held company, Honoraria; AbbVie, Amgen, Astrazeneca, Caribou Biosciences, Celgene, Daiichi Sankyo, Ellipses pharma, Geron, GSK, Glycomimetics, Janssen, Jasper Pharmaceuticals, Jazz Pharmaceuticals, Molecular Partners, Oncoverity: Consultancy; Novartis, Pfizer, Roche, GlaxoSmithKline, BMS, Syndax, Rigel: Consultancy. Wang: Astellas: Consultancy, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sellas: Membership on an entity's Board of Directors or advisory committees; Schrodinger: Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; NuProbe: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kura: Speakers Bureau; Qiagen: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Immunogen: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees; UptoDate: Other: Section Editor; Dava Oncology: Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Award Committee, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Research Funding, Speakers Bureau. Amaya: Bristol Myers Squibb: Honoraria. Madanat: Taiho Oncology, Rigel Pharmaceuticals, Novartis: Consultancy; OncLive, MD Education, Sierra Oncology, Stemline, MorphoSys: Consultancy; Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences and Novartis: Other: Advisory Board; Blueprint Medicines, MD Education, and Morphosys: Other: travel; BMS, Kura Oncology, BluePrint Medicines, Geron: Consultancy. Badar: pfizer: Other: Advisory board; Takeda: Other: advisory board ; Morphosys: Other: Advisory Board. Sallman: Agios: Consultancy; Abbvie: Consultancy; Axiom: Consultancy; Gilead: Consultancy; Celyad: Consultancy; Froghorn: Consultancy; Incyte: Consultancy; Intellisphere, LLC: Consultancy; Johnson & Johnson: Consultancy; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; NextTech: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AvenCell: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Dark Blue Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Membership on an entity's Board of Directors or advisory committees; NKARTA: Membership on an entity's Board of Directors or advisory committees; Orbital Therapeutics: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Apera: Research Funding; Jazz: Research Funding. Enjeti: RACE Oncology: Consultancy, Honoraria; Amgen: Honoraria; Jazz: Honoraria; Servier: Honoraria; Astellas: Honoraria, Speakers Bureau; AbbVie: Speakers Bureau; Otsuka: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria. Hiwase: Abbvie: Honoraria; Astella Pharma: Honoraria; Otsuka: Honoraria. Diez-Campelo: SYROS: Membership on an entity's Board of Directors or advisory committees; CURIS: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board fees; ASTEX/OTSUKA: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL TO MEETINGS; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; KEROS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Other: Travel reimbursement; BLUEPRINT MEDICINES: Consultancy, Membership on an entity's Board of Directors or advisory committees; AGIOS: Consultancy, Membership on an entity's Board of Directors or advisory committees; HEMAVAN: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees. Valcarcel: Janssen: Honoraria, Speakers Bureau; Jazz Pharmaceuticials: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Gebro: Honoraria, Speakers Bureau; Agios: Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; Astellas: Consultancy, Honoraria; AbbVie: Consultancy, Other: Meeting and travel accommodation; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; SOBI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Speakers Bureau. Haferlach: Abbvie: Consultancy, Honoraria. Pleyer: AbbVie: Honoraria; BMS: Honoraria; Otsuka: Honoraria. Santini: Ascentage, AbbVie, Bristol Myers Squibb, CTI BioPharma, Geron, Gilead, Novartis, Servier, Syros Pharmaceuticals: Other: Advisory Board. Ogawa: Otsuka Pharmaceutical Co., Ltd.: Research Funding; Nihonshinyaku Co., Ltd.: Other: Donation; Nanpuh Hospital: Other: Endowed chair; Chordia Therapeutics Inc.: Consultancy, Other: Endowed chair, Research Funding; Asahi Genomics Inc: Current equity holder in publicly-traded company; Eisai Co., Ltd.: Consultancy, Research Funding. Nannya: Bristol Meyer Squibb: Consultancy; Takeda Pharmaceutical: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Bristol Meyer Squibb: Speakers Bureau; KyowaHakko Kirin: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau; Nippon Shinyaku: Speakers Bureau; Otsuka Pharmaceutical: Speakers Bureau; Astra-Zeneca: Speakers Bureau; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Otsuka Pharmacutical: Consultancy. Della Porta: Bristol Myers Squibb: Consultancy. Komrokji: Janssen: Consultancy; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servio: Honoraria; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servio: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Taiho: Membership on an entity's Board of Directors or advisory committees. Zeidan: Shattuck Labs: Research Funding; Rigel: Consultancy, Honoraria; Faron: Consultancy, Honoraria; Astex: Research Funding; Karyopharm: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Orum: Consultancy, Honoraria; Notable: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Kura: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Research Funding; Keros: Consultancy, Honoraria; Lava Therapeutics: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Treadwell: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Akeso Pharma: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Hikma: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Zentalis: Consultancy, Honoraria; Syndax: Consultancy, Honoraria; Taiho: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Chiesi: Consultancy, Honoraria; Vinerx: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Schroedinger: Consultancy, Honoraria; BioCryst: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Consultancy, Honoraria; Medus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Geron: Consultancy, Honoraria, Research Funding; ALX Oncology: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sumitomo: Consultancy, Honoraria; Syros: Consultancy, Honoraria, Research Funding. Stahl: GSK: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Kymera: Membership on an entity's Board of Directors or advisory committees; Sierra Oncolgy: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees.

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^*signifies non-member of ASH

664 Impact of Response to Hypomethylating Agent-Based Therapy on Survival Outcomes in the Context of Baseline Clinical-Molecular Risk and Transplant Status in Patients with Myelodysplastic Syndromes/Neoplasms (MDS): An Analysis from the International Consortium for MDS (icMDS) Validate Database