Clinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database

Getz, Ted

Oral and Poster Abstracts
637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II

Research, MDS, Adult, Clinical Research, Chemotherapy, Chronic Myeloid Malignancies, Diseases, Treatment Considerations, Registries, Non-Biological therapies, Myeloid Malignancies, Technology and Procedures, Study Population, Human, Molecular testing

Ted M. Getz, MD¹, Tariq Kewan, MD², Jan Philipp Bewersdorf, MD^3,4, Jessica M. Stempel, MD², Luca Lanino, MD⁵, Wei Wei, MD, PhD⁶, Najla H. Al Ali, Ms⁷^*, Amy E. DeZern, MD, MHS⁸, Mikkael A. Sekeres, MD⁹, Geoffrey L. Uy, MD¹⁰, Hetty E. Carraway, MD, MBA¹¹, Pinkal Desai¹², Elizabeth A. Griffiths, MD¹³, Eytan M. Stein, MD¹⁴, Andrew M. Brunner, MD¹⁵, Christine M. McMahon, MD¹⁶, Rory M. Shallis, MD¹⁷, Joshua F. Zeidner, MD¹⁸, Michael R. Savona, MD¹⁹, Somedeb Ball, MD¹⁹, Namrata S. Chandhok, MD²⁰, Constantine Logothetis, MD²¹, Aram Bidikian, MD², Gail J. Roboz, MD²², Benjamin Rolles, MD^23,24, Eunice S. Wang, MD²⁵, Amyah C. Harris¹⁵^*, Maria L Amaya, MD, PhD²⁶, Hayley Hawkins¹⁹^*, Justin Grenet, MD, MPhil¹², Zhuoer Xie, MD, MS²⁷, Yazan F. Madanat, MD²⁸, Yasmin Abaza, MD²⁹, Talha Badar, MD³⁰, Torsten Haferlach, MD³¹, Jaroslaw Maciejewski³², David Sallman, MD⁷, Anoop K Enjeti, MBBS, FRCPA, MD, MRCP³³, Kamal Al-Rabi, MD³⁴^*, Khalid Halahleh, M.B.S.S.³⁴^*, Devendra Hiwase, MD, MBBS, PhD, FRACP, FRCPA³⁵, Maria Diez-Campelo, MD, PhD³⁶^*, David Valcarcel, MD, PhD³⁷, Claudia Haferlach, MD³¹, Lisa Pleyer, MD³⁸^*, Ioannis Kotsianidis, PhD³⁹, Vasiliki Pappa, MD, PhD⁴⁰, Valeria Santini, MD⁴¹, Angela Consagra, MD⁴²^*, Aref Al-Kali, MD⁴³, Seishi Ogawa, MD, PhD⁴⁴, Yasuhito Nannya, MD, PhD⁴⁴, Maximilian Stahl, MD⁴⁵, Matteo Giovanni Della Porta, MD⁴⁶^*, Rami S. Komrokji, MD²⁷ and Amer M. Zeidan, MBBS, MHS²

¹Department of Internal Medicine, Section of Hematology, Yale University, Jersey City, NJ
²Department of Internal Medicine, Section of Hematology, Yale University, New Haven, CT
³Department of Internal Medicine, Section of Hematology, Yale School of Medicine - Yale Cancer Center, New Haven, CT
⁴Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY
⁵IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
⁶School of Public Health, Department of Biostatistics, Yale University, New Haven, CT
⁷Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
⁸Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore
⁹Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
¹⁰Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
¹¹Department of Hematology and Medical Oncology, Taussig Cancer Institute, Leukemia Program, Cleveland Clinic, Cleveland, OH
¹²Weill Cornell Medicine, New York, NY
¹³Roswell Park Comprehensive Cancer Center, Buffalo, NY
¹⁴Department of Medicine; Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY
¹⁵Division of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
¹⁶University of Colorado School of Medicine, Denver, CO
¹⁷Department of Internal Medicine, Section of Hematology, Yale School of Medicine - Yale Cancer Center, Killingworth, CT
¹⁸Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill
¹⁹Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
²⁰Sylvester Comprehensive Cancer Center, University of Miami-Miller School of Medicine, Miami, FL
²¹Division of Oncology, Washington University School of Medicine, Saint Louis, MO
²²Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY
²³Division of Hematology, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA
²⁴Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²⁵Leukemia Service, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
²⁶University of Colorado, Aurora, CO
²⁷Department of Malignant Hematology, H Lee Moffitt Cancer Center, Tampa, FL
²⁸Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
²⁹Northwestern University, Chicago, IL
³⁰Division of Hematology-Oncology, Mayo Clinic, Jacksonville
³¹MLL Munich Leukemia Laboratory, Munich, Germany
³²Taussig Cancer Center, Cleveland, OH
³³Department of Haematology, Calvary Mater Hospital, Waratah, NSW, Australia
³⁴King Hussein Cancer Center, Amman, Jordan
³⁵Royal Adelaide Hospital, Adelaide, SA, Australia
³⁶Hematology Department, Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, Salamanca, Spain
³⁷Department of Hematology and Oncology, Hospital Universitario Vall d'Hebron, Barcelona, Spain
³⁸3rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Oncologic Center, Salzburg, Austria
³⁹Democritus University of Thrace, Department of Hematology, University Hospital of Alexandroupolis, Alexandroupolis, Greece, Alexandroupolis, Greece
⁴⁰Hematology Division, Second Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
⁴¹MDS Unit, Hematology, AOU Careggi ‐ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
⁴²MDS Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
⁴³Mayo Clinic, Rochester, MN
⁴⁴Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
⁴⁵Dana Farber Cancer Institute, Boston, MA
⁴⁶Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy

Introduction

The International Prognostic Scoring System (IPSS) and its revised version (IPSS-R) were developed using datasets from patients (pts) with untreated MDS. The cytogenetic risk groups used in IPSS-R were expanded to 5 groups from the 3 used in IPSS. Among the new groups introduced in IPSS-R is the “very complex” karyotype (VCK) where ≥4 karyotypic abnormalities are seen compared to “complex karyotype (CK)” with only 3 abnormalities. However, the prognostic impact of VCK vs CK, as well as individual cytogenetic abnormalities and TP53 mutation (TP53^mut) status within the CK and VCK subgroups in pts with MDS treated with hypomethylating agents (HMAs) has not been well studied. Hence, we analyzed these questions in a large cohort of HMA-treated MDS pts in the icMDS VALIDATE database.

Methods

The icMDS VALIDATE database contains MDS pts treated with frontline HMA monotherapy or HMA-based combinations from 22 specialized international centers. Pts with unknown HMA type, date of HMA initiation, missing age, missing sex, missing cytogenetic data, bone marrow or peripheral blood blasts ≥20%, or missing survival status were excluded. We performed time-to-event analyses using the Kaplan-Meier method and compared groups by the log-rank test. We measured overall survival (OS) from time of HMA initiation. VALIDATE protocol was exempted, acknowledged, or approved by all centers’ IRBs. VALIDATE is supported by an independent grant from Abbvie.

Results

A total of 1940 pts were included. Median age was 70 (range: 18-99) years and 66% were men. According to IPSS-R cytogenetic risk groups, 1.9% (37) were very good, 43.4% (841) good, 15.5% (301) intermediate, 11.6% (226) poor, and 27.6% (535) very poor. By HMA type, 71% of pts were treated with azacitidine, 14% with decitabine, 6% with HMA and venetoclax, and 9% with another HMA combination. Approximately 28% of pts underwent allogeneic hematopoietic stem cell transplant (alloHSCT). The IPSS-R cytogenetic risk groups had different OS (p<0.001) with median OS (mOS; months [mo], 95% CI) as follows: very good (43.4, 34.7-72.5), good (41.7, 36.4-46.8), intermediate (24.5, 23.1-32.4), poor (24.2, 19.2-28.5), and very poor (13.6, 12.5-14.5). The difference remained significant (p=0.001) after censoring at time of alloHSCT with mOS as follows: very good (40.4, 23.2-64.3), good (24.3, 22.2-26.3), intermediate (19.3, 15.1-22.2), poor (12.2, 10.3-14.8), and very poor (9.1, 8.2-19.7). Interestingly, the difference between mOS for intermediate and poor risk cytogenetics became more apparent after censoring at time of alloHSCT.

Next, we compared the outcomes of pts with CK and VCK to non-complex karyotype (NCK) MDS. The mOS for pts with VCK MDS (13.6 mo, 12.5-14.5) was worse compared to pts with CK (19.9 mo, 19.9-16.8; p=0.004) and NCK (36.1 mo, 32.7-37.8; p<0.001) MDS. Among the 1458 pts with available molecular data, more pts with VCK (75%, 330) MDS had a concurrent TP53^mut compared to pts with CK (40%, 21; p<0.001) and NCK (7%, 64 p<0.001) MDS. Considering only patients with TP53^mut MDS, mOS for pts with VCK (12.2, 11.1-13.9) was worse compared with NCK (24.2, 16-1-53.1; p<0.001) but not with CK (19.9, 9.5-NR; p=0.9); the difference between CK and NCK was not significant (p=0.16). Among pts with TP53 wildtype (TP53^WT) MDS, VCK (15.0, 13.2-18.2) had a similar mOS to TP53^WT CK (18.8, 12.6-41.1; p=0.19) while both groups had worse mOS compared to TP53^WT NCK (33.4, 30.1-37.0) (p=0.01). In a survival analysis of 616 pts with MDS with ≥3 cytogenetic abnormalities, -17/del(17p) (12.8 mo; p=0.009), inv(3)/t(3q)/del(3q) (10.9 mo; p=0.006), and del(7q) (12.1mo; p=0.024), though not -7 (12.6mo; p=0.23), were associated with lower mOS compared to the pts with MDS without these abnormalities (14.3mo).

Conclusions

Using one of the largest databases of HMA-treated MDS pts, we show that IPSS-R cytogenetic risk categories associate with significantly different survivals among HMA-treated MDS pts, even after censoring at time of alloHSCT. Importantly, VCK MDS was associated with worse mOS compared to CK and NCK MDS but not in pts with a concurrent TP53^mut. Among pts with MDS with ≥3 chromosomal abnormalities, having -17/del(17p), inv(3)/t(3q)/del(3q), or del(7q) was associated with worse survival.

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

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3219 Clinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database