-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1003 A Molecular-Based Ecosystem to Improve Personalized Medicine in Patients with Chronic Myelomonocytic Leukemia (CMML)

Program: Oral and Poster Abstracts
Type: Oral
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Defining and Treating Chronic Myelomonocytic Leukemia
Hematology Disease Topics & Pathways:
Research, MDS, Artificial intelligence (AI), Adult, Elderly, Clinical Research, Chronic Myeloid Malignancies, CMML, Diseases, Therapy sequence, Real-world evidence, Treatment Considerations, Myeloid Malignancies, Technology and Procedures, Study Population, Human
Monday, December 9, 2024: 4:30 PM

Luca Lanino, MD1,2, Anthony M. Hunter, MD3, Nico Gagelmann, M.D.4*, Marie Robin, MD5*, Claudia Sala, PhD6*, Daniele Dall'Olio, PhD7*, Carmelo Gurnari, MD, PhD8, Lorenzo Dall'Olio, PhD9*, Yu-Hung Wang, MD10,11*, Lisa Pleyer, MD12*, Blanca Xicoy, MD13*, Guillermo Montalban-Bravo, MD14, Lee-Yung Shih, MD15, Tamanna Haque, MD16*, Omar Abdel-Wahab, MD17, Klaus Geissler, MD18*, Alex Bataller, MD, PhD14*, Alexandre Bazinet, MD14*, Manja Meggendorfer, PhD19, Ilaria Carola Casetti, MD, PhD20*, Elisabetta Sauta, PhD21*, Erica Travaglino, BS22*, Laura Palomo, PhD23*, Lurdes Zamora, PhD24*, David Quintela25*, Andres Jerez, MD, PhD26*, Elena Cornejo27*, Paloma Garcia Martin27*, Marina Díaz-Beyá, MD, PhD28*, Alejandro Avendaño Pita29*, Veronica Roldan30*, Dolly Viviana Fiallo Suarez31*, Estefania Cerezo Velasco, MD32*, Marisa Calabuig33*, Esperanza Such, PhD34*, Guillermo Sanz, MD, PhD35, Anne Sophie Kubasch, MD36, Cristina Castilla-Llorente, MD37*, Claude-Éric Bulabois, MD38*, Laetitia Souchet39*, Hussein Awada40, Massimo Bernardi, MD41*, Patrizia Chiusolo, MD, PhD42*, Antonio Curti, MD, PhD43, Luisa Giaccone, MD, PhD44*, Francesco Onida, MD20, Lorenza Maria Borin, MD45*, Francesco Passamonti, MD46*, Elisa Diral, MD47*, Vladan Vucinic, MD48*, Gregorio Maria Bergonzi, MD47*, Maria Teresa Voso, MD49, Hsin-An Hou, MD, PhD, MSc50*, Wen-Chien Chou, MD, PhD51, Chi-Yuan Yao, MD51*, Chien-Chin Lin, MD, PhD50*, Hwei-Fang Tien, MD, PhD52, Alessia Campagna, MD21*, Marta Ubezio, MD1*, Antonio Russo, MD1*, Gabriele Todisco, MD2,21*, Giulia Maggioni, MD21*, Cristina Astrid Tentori, MD21*, Alessandro Buizza, MD2,21*, Gianluca Asti, MSc21*, Matteo Zampini, PhD1*, Elena Riva, PhD1*, Mattia Delleani21*, Angela Consagra, MD53*, Francesca Ficara, PhD21*, Armando Santoro, MD54*, Luciana Carota, PhD6*, Tiziana Sanavia, PhD55*, Cesare Rollo, PhD55*, Ahmad Kiwan, MD56, Jennifer VanOudenhove, PhD57, Piero Fariselli, PhD55*, Najla H. Al Ali, Ms58*, David Sallman, MD58, Wolfgang Kern, MD59, Guillermo Garcia-Manero, MD14, Swapna Thota, MD60, Elizabeth A. Griffiths, MD61, Matilde Yung Follo, PhD62*, Carlo Finelli, MD63*, Uwe Platzbecker, MD64, Francesc Sole, PhD65, Maria Diez-Campelo, MD, PhD66*, Jaroslaw Maciejewski40, Rafael Bejar, MD, PhD67, Felicitas R. Thol, MD68, Nicolaus Kröger, MD69*, Pierre Fenaux, MD70, Raphael Itzykson71, Timothy Aaron Graubert, MD72, Michaela Fontenay, MD, PhD73*, Amer M. Zeidan, MBBS, MHS74, Rami S. Komrokji, MD75, Valeria Santini, MD76, Torsten Haferlach, MD59, Ulrich Germing, MD77*, Saverio D'Amico, MSc21*, Gastone Castellani, PhD78*, Mrinal M. Patnaik, MD, MBBS79, Eric Solary, MD80*, Eric Padron, MD58 and Matteo Giovanni Della Porta, MD2,21*

1IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA
4Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5Hopital Saint Louis, APHP, Paris, France
6University of Bologna, Bologna, Italy
7IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
8Cleveland Clinic Foundation, Cleveland, OH
9Department of Physics and Astronomy, University of Bologna, Bologna, Italy
10Department of Internal Medicine, Fra-Eastern Memorial Hospital, Taipei, Taiwan
11Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
123rd Medical Dept. with Haematology, Medical Oncology, Haemostaseology, Rheumatology and Infectiology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
13Hematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
14Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
15Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
16Memorial Sloan Kettering Cancer Center, New York, NY
17Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
18Hospital Hietzing, Vienna, Austria
19MLL Munich Leukemia Laboratory, Munich, Bavaria, Germany
20Hematology Unit, ASST Fatebenefratelli Sacco, Milan, Italy
21IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
22Policlinico San Matteo, Pavia, Italy
23Department of Hematology, Vall d’Hebron University Hospital, Barcelona, Spain
24Haematology Department, ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
25Institut Català d’Oncologia, Badalona, Spain
26Department of Hematology, Vall d'Hebron University Hospital, Barcelona, Spain
27Hospital Clínico San Cecilio, Granada, Spain
28Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
29Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain
30Hospital Universitario Cruces, Bilbao, Spain
31Hospital Negrin, LAS PALMAS, Spain
32Hematology Department, Consorcio Sanitario de Terrassa, Terrassa, Spain
33Hospital Clínico Universitario de Valencia, Valencia, Spain
34Hematology Research Group, Hospital Universitari I PolitèCnic La Fe; Dep. of Hematology, University, Valencia, Spain
35Hospital Universitario y Politécnico e Instituto de Investigación Sanitaria La Fe, Valencia, Spain
36Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany
37Gustave Roussy Cancer Campus, Villejuif, France
38Hematology Department, Grenoble University Hospital, Grenoble, France
39Pitie Salpetriere Hospital, APHP, Sorbonne Universite, Paris, FRA
40Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
41Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milano, Italy
42UOC Ematologia e Trapianto Cellule Staminali Emopoietiche, Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
43IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
44Univesity of Torino, AOU Città Della Salute E Della Scienza Di Torino,, Torino, ITA
45Hematology Division and Bone Marrow Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
46Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
47Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy
48Department for Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University of Leipzig, Leipzig, Saxony, Germany
49Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
50Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
51Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
52Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan
53MDS Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
54IRCCS Humanitas Research Hospital, Rozzano, Italy
55Computational Biomedicine Unit, Department of Medical Sciences, University of Torino, Turin, Italy
56Yale University, New Haven, CT
57Department of Internal Medicine, Section of Hematology, Yale University, New Haven, CT
58Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
59MLL Munich Leukemia Laboratory, Munich, Germany
60Department of Medicine, University of Tennessee Health Science Center, MEMPHIS, TN
61Roswell Park Comprehensive Cancer Center, Buffalo, NY
62Department of Biomedical and Neuromotor Sciences, Cellular Signalling Laboratory, University of Bologna, Bologna, Italy
63IRCCS Azienda Ospedaliero-Universitaria di Bologna, Hematology Institute “L. e A. Seràgnoli”, Bologna, Italy
64Department for Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University of Leipzig Medical Center, Leipzig, Germany
65Myelodysplastic Syndromes Research Group, Institut De Recerca Josep Carreras, Badalona, Barcelona, Spain
66Hospital Clínico Universitario de Salamanca, Salamanca, Spain
67University of California, San Diego, La Jolla, CA
68Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
69University Hospital Eppendorf, Hamburg, Germany, Hamburg, Germany
70Service Hématologie Seniors, Assistance Publique des Hôpitaux de Paris (APHP), Université Paris Cité, Paris, France
71Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique (CNRS), Paris, France, Paris, France
72Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA
73Laboratory of Hematology, Université Paris Cité and Assistance Publique-Hôpitaux de Paris Centre, Hôpital Cochin, Groupe Francophone des Myelodysplasies, Paris, France
74Department of Internal Medicine, Section of Hematology, Yale School of Medicine - Yale Cancer Center, New Haven, CT
75Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
76MDS Unit, Hematology, AOUC, University of Florence, Florence, Italy
77Department of Hematology, Oncology and Clinical Immunology, University Medical Center Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
78Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
79Mayo Clinic, Rochester, MN
80Inserm UMR866, Villejuif Cedex, France

Background. Study of myeloid neoplasms (MN) has been rapidly transformed by genome characterization. Gene mutations have been reported to influence disease phenotype and risk of disease progression, and the evaluation of mutational status can provide valuable insights to improve the decision-making process. In this international study, we evaluated the clinical impact of mutational screening in patients with CMML, which is characterized by significant clinical and genomic heterogeneity, including a substantial proportion of patients with poor outcomes and unmet needs. Currently, only limited molecular information has been incorporated into CMML classification and prognostication.

Methods. We retrospectively collected 3182 CMML patients. We used MOSAIC, an AI-based framework for multimodal analysis in rare cancers (PMID: 38875514) to develop innovative, molecular-based tools for classification and prognostication. An independent validation of the results on 516 prospectively collected patients was performed.

Results. Bayesian Networs and Hierarchical Dirichlet Processes were used to identify genomic associations and define a CMML molecular classification. We identified 11 clusters with distinct clinical and genomic features, including splicing machinery, signal transduction and tyrosine kinase pathways aberrations, and high-risk molecular signatures (i.e., AML-like and TP53 mutations). Up to 15% of patients showed clear genomic overlap with other MN. Importantly, extensive multi-color flow cytometry on T lymphocytes, NK and myeloid cells (BD FACSymphony A5 Cell Analyzer) revealed specific immunologic and inflammation signatures associated with molecular subgroups.

We then integrated molecular and clinical information to build an international CMML Prognostic Scoring System (iCPSS). We assessed the performance of different statistical and AI-based methods; L1-penalized Cox Model resulted as the best performing method. Selected features included hematological parameters (WBC, Hb, PLT and marrow blasts), cytogenetic abnormalities, and mutations in 10 genes (ASXL1, DNMT3A, EZH2, NRAS, RUNX1, SETBP1, STAG2, TET2, TP53, U2AF1). By Bayesian thresholds optimization, we identified 5 risk classes (i.e., very-low, low, intermediate, high and very-high) with median overall survival (OS) ranging from 99 to 9 months (P<.001), and median leukemia-free survival (LFS) ranging from 210 to 18 months (P<.001). iCPSS provided better patient discrimination across all clinical endpoints compared to currently available prognostic tools, with a Concordance Index (CI) for OS of 0.75 versus 0.62-0.64, respectively. Notably, compared to available scoring systems, up to 40% of patients were reassigned to higher or lower risk classes by the iCPSS. External validation on an independent prospective cohort confirmed that the performance of iCPSS is superior to existing prognostic models (CI for OS 0.71 vs 0.54-0.61, respectively)

To demonstrate the clinical utility of iCPSS, we focused on 753 patients who underwent allogeneic stem cell transplantation (HSCT). In multivariable analysis, iCPSS stratified the probability of OS post-HSCT (P<.001) and identified groups of patients with different probabilities of disease relapse, ranging from 9% to 62% (P<.001). We employed a clinical- and genomic-based decision support system (PMID: 38723212) to determine the optimal timing of HSCT. Preliminary analyses indicated that higher-risk patients according to iCPSS (i.e., intermediate, high, and very high) benefit from an immediate HSCT strategy. Lower-risk patients (i.e., very low and low) had life expectancy maximized with delayed HSCT. Modeling decision analysis using iCPSS compared to conventional scores, resulted in a change in transplantation policy for a significant proportion of patients (up to 25%).

Conclusion. Molecular information significantly improves the classification of CMML patients, providing a basis for refining diagnostic boundaries with other MN and for a more rational inclusion of patients in clinical trials. The iCPSS demonstrated superior performance over currently available scoring systems and improved HSCT decision making process.

Disclosures: Hunter: GSK: Consultancy, Honoraria; PharmaEssentia: Consultancy, Honoraria; Blueprint Medicines: Consultancy, Honoraria, Research Funding; Sobi​ (formerly CTI biopharma): Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Cogent Biosciences: Research Funding; Ascentage Pharma: Research Funding; Syntrix Biosystems: Research Funding; Novartis: Research Funding; PharmaEssentia: Research Funding. Robin: Novartis: Other: research support; Abbvie: Other: research support; Medac: Other: research support; Neovii: Other: research support. Pleyer: BMS: Honoraria; AbbVie: Honoraria; Otsuka: Honoraria. Xicoy: BMS: Honoraria. Montalban-Bravo: Takeda: Research Funding; Rigel: Research Funding. Shih: PhamaEssentia: Honoraria; Novartis, Taiwan: Research Funding; GSK: Honoraria; Celgene: Research Funding. Abdel-Wahab: Minovia Therapeutics: Consultancy, Research Funding; Codify Therapeutics: Consultancy, Current equity holder in private company, Research Funding; Nurix Therapeutics: Research Funding. Geissler: Otsuka: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Beigene: Honoraria; Celgene: Honoraria; BMS: Honoraria. Zamora: Celgene/BMS, Incyte, Novartis: Other: Lurdes Zamora reports grants and personal fees from Celgene/BMS, Incyte, and Novartis outside the submitted work.. Jerez: Aztrazeneca: Research Funding; GILEAD: Research Funding; Novartis: Consultancy; BMS: Consultancy. Díaz-Beyá: BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Abbvie: Consultancy. Sanz: Novartis, BMS, J&J, Takeda, Amgen, Menarini, Bayer, Pfizer: Other; BMS: Research Funding; AstraZeneca, GSK: Consultancy, Honoraria; Novartis, ExCellera: Speakers Bureau. Kubasch: BMS: Honoraria; Curis: Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Curti: Pfizer: Honoraria, Research Funding; Menarini stemline: Honoraria; Abbvie: Honoraria; Jazz Pharmaceutics: Honoraria. Giaccone: Abbvie: Honoraria. Onida: Menarini-stemline: Speakers Bureau; kyowa: Speakers Bureau; MEDAC: Speakers Bureau; takeda: Speakers Bureau. Passamonti: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vucinic: Gilead/Kite, Janssen, BMS Celgene, Novartis: Consultancy, Honoraria; Amgen: Honoraria, Other: Travel grant. Voso: Celgene/BMS: Other: Research support, Advisory Board, Speakers Bureau; Astra Zeneca: Speakers Bureau; Abbvie: Speakers Bureau; Syros: Other: Advisory Board; Jazz: Other: Advisory Board, Speakers Bureau; Astellas: Speakers Bureau; Novartis: Other: Research support, Speakers Bureau. Hou: Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding; PharmaEssentia: Consultancy, Honoraria, Other: Travel fees; Synmosa: Consultancy, Honoraria, Other: Travel fees; Panco healthcare Co: Consultancy, Honoraria, Other: Travel fees; AstraZeneca: Consultancy, Honoraria, Other: Travel fees; Novartis: Consultancy, Honoraria, Other: Travel fees; IQVIA: Consultancy, Honoraria, Other: Travel fees; Astellas: Consultancy, Other: Travel fees, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel fees, Research Funding; CSL Behring: Consultancy, Honoraria, Other: Travel fees; Sandoz: Consultancy, Honoraria, Other: Travel fees; TSH Biopharm: Consultancy, Honoraria, Other: Travel fees; Lotus: Consultancy, Honoraria, Other: Travel fees; Kirin: Consultancy, Honoraria, Other: Travel fees; Johnson & Johnson: Consultancy, Honoraria, Other: Travel fees; Eli Lilly: Consultancy, Honoraria, Other: Travel fees; BMS: Consultancy, Honoraria, Other: Travel fees, Research Funding; GSK: Honoraria; Pfizer: Consultancy, Honoraria, Other: Travel fees; Kirin: Research Funding; Zuellig Pharma: Consultancy, Honoraria, Other: Travel fees; Ono: Consultancy, Honoraria, Other: Travel fees; Roche: Consultancy, Honoraria, Other: Travel fees; Chugai: Consultancy, Honoraria, Other: Travel fees; TTY Biopharm Company: Consultancy, Honoraria, Other: Travel fees ; Merck Sharp & Dohme: Consultancy, Honoraria, Other: Travel fees; Takeda: Consultancy, Honoraria, Other: Travel fees; Daiichi Sankyo: Consultancy, Honoraria, Other: Travel fees; BeiGene: Consultancy, Honoraria, Other: Travel fees; PharmaEssentia: Research Funding. Santoro: Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Abb-vie: Speakers Bureau; Incyte: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Arqule: Speakers Bureau; Sanofi: Consultancy; Roche: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EISAI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Beigene: Speakers Bureau; Astrazeneca: Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau. Sallman: Abbvie: Consultancy; Agios: 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. Garcia-Manero: Helsinn: Research Funding; Novartis: Research Funding; Janssen: Research Funding; Curis: Research Funding; Bristol Myers Squibb: Other: Personal fees, Research Funding; Forty Seven: Research Funding; Genentech: Research Funding; Aprea: Research Funding; Astex: Other: Personal fees; Merck: Research Funding; H3 Biomedicine: Research Funding; Onconova: Research Funding; Astex: Research Funding; AbbVie: Research Funding; Helsinn: Other: Personal fees; Amphivena: Research Funding; Genentech: Other: Personal fees. Thota: Sobi Inc, Novartis, Alexion, pharmaessentia: Membership on an entity's Board of Directors or advisory committees. Griffiths: Partner Therapeutics: Consultancy; Picnic Health: Consultancy; Astex Pharmaceuticals/Taiho Oncology/Otsuka: Consultancy, Research Funding; MDS International Foundation: Honoraria; Alexion Pharmaceuticals/ AstraZeneca Rare Disease: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Blueprint Medicines: Research Funding; Celldex Pharmaceuticals: Research Funding; CTI Biopharma: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; MedscapeLive: Honoraria; MediCom Worldwide: Honoraria; Novartis: Consultancy, Research Funding; AAMDS: Honoraria; Abbvie: Consultancy; Servier: Consultancy; MJH Health: Honoraria; Physicians Educational Resource: Honoraria; ASH: Honoraria; NextCure: Research Funding; Apellis Pharmaceuticals: Consultancy, Research Funding; Takeda Oncology: Consultancy. Finelli: Celgene BMS: Consultancy; Novartis: Consultancy; Takeda: Consultancy. Platzbecker: Amgen: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Research Funding; Curis: Consultancy, Honoraria, Research Funding; Geron: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Novartis: Consultancy, Research Funding. Diez-Campelo: SYROS: 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; 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; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board fees; Gilead: Other: Travel reimbursement; HEMAVAN: Membership on an entity's Board of Directors or advisory committees; CURIS: Membership on an entity's Board of Directors or advisory committees; AGIOS: Consultancy, Membership on an entity's Board of Directors or advisory committees; KEROS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bejar: Aptose Biosciences: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Thol: Astellas: Honoraria; Rigel: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Kröger: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Neovii: 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; Therakos: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; DKMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Provirex: Consultancy. Fenaux: Agios: Research Funding; AbbVie: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astex: Research Funding; Servier: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding. Itzykson: Abbvie: Research Funding; Advesya: Research Funding. Zeidan: Agios: Consultancy, Honoraria; Akeso Pharma: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Schroedinger: Consultancy, Honoraria; Syndax: Consultancy, Honoraria; Taiho: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Treadwell: Consultancy, Honoraria; Medus: Consultancy, Honoraria; Hikma: Consultancy, Honoraria; Vinerx: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Syros: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Rigel: Consultancy, Honoraria; Sumitomo: Consultancy, Honoraria; Orum: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Geron: Consultancy, Honoraria, Research Funding; Shattuck Labs: Research Funding; Kura: Consultancy, Honoraria, Research Funding; Astex: Research Funding; Keros: Consultancy, Honoraria; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Research Funding; Notable: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Lava Therapeutics: Consultancy, Honoraria; BioCryst: Consultancy, Honoraria; ALX Oncology: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Zentalis: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Chiesi: Consultancy, Honoraria; Faron: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Komrokji: DSI: 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; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding; Keros: 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; Janssen: Consultancy; Servio: Honoraria; Servier: 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; Genentech: Consultancy; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Taiho: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: 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; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; Servio: Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: 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; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Santini: Ascentage, AbbVie, Bristol Myers Squibb, CTI BioPharma, Geron, Gilead, Novartis, Servier, Syros Pharmaceuticals: Other: Advisory Board. Germing: JAZZ: Research Funding; Novatis: Honoraria; BMS: Honoraria; BMS: Research Funding; Abbvie: Research Funding. Patnaik: Kura Oncology: Research Funding; Epigenetix: Research Funding; StemLine: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Polaris: Research Funding; Solu therapeutics: Research Funding. Solary: PEPKON: Research Funding; NOVARTIS: Speakers Bureau. Della Porta: Bristol Myers Squibb: Consultancy.

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*signifies non-member of ASH