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3618 Post Allogeneic Stem Cell Transplant Outcomes Following Response to Hypomethylating Agent Therapy in Myelodysplastic Syndromes Are Predicted By Persistent International Prognostic Scoring System-Molecular Risk

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, health outcomes research, Diseases, Myeloid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Stacey M Frumm, md1*, Haesook T. Kim, PhD2, Amar H Kelkar, MD3, Vincent T. Ho, MD4*, Mahasweta Gooptu, MD3, Christopher James Gibson, MD3, John Koreth, MD, MBBS, PhD, DPhil3, Roman M. Shapiro, MD3, Rizwan Romee, MD5, Sarah Nikiforow, MD, PhD3, Joseph H. Antin, MD6, Robert J. Soiffer, MD3, Benjamin Rolles, MD7, Shai Shimony, MD8*, Jan Philipp Bewersdorf, MD9, Tariq Kewan, MBBChir10, Abdulrahman Alhajahjeh, MD11*, Marlise R. Luskin, MD4, Jacqueline S. Garcia, MD8, Evan C. Chen, MD3, Andrew A. Lane, MD, PhD12, Martha Wadleigh, MD3, Eric S. Winer, MD3, Richard M Stone, MD3, Daniel J. DeAngelo3, Amer M. Zeidan, MBBS, MHS13, Coleman Lindsley, MD, PhD3, Corey Cutler3 and Maximilian Stahl, MD4

1Brigham and Women's Hospital, Brookline, MA
2Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
3Dana-Farber Cancer Institute, Boston, MA
4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
5Dana Farber Cancer Institute, Boston, MA
6Dana-Farber Cancer Inst. Brigham & Women's Hospital, Boston, MA
7Division of Hematology, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA
8Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
9Memorial Sloan Kettering Cancer Center, New York, NY
10Department of Internal Medicine, Section of Hematology, Yale University, New Haven, CT
11University of Jordan, Amman, Jordan
12Department of Medical Oncology, Dana-Farber Cancer Institute, Inc., Boston, MA
13Section of Hematology, Department of Internal Medicine, Yale University School of Medicine - Yale Cancer Center, New Haven, CT

Introduction: The International Prognostic Scoring System-Molecular (IPSS-M) (Bernard NEJM Evidence 2022) and the 2023 International Working Group (IWG) response criteria for myelodysplastic syndrome (MDS) (Zeidan Blood 2023) are used to more accurately assess prognosis and therapeutic response in MDS. However, it is unknown if these tools can be used to predict outcomes post-allogeneic hematopoietic stem cell transplant (HCT). We sought to understand the impact of pre-HCT IPSS-M on post-HCT outcomes in patients (pts) with MDS who responded to hypomethylating agent (HMA) therapy.

Methods: Pts with MDS treated with HMA (azacitidine or decitabine) who received an HCT post-HMA at Dana-Farber Cancer Institute from January 2014 to December 2020 were included. Response to HMA was assessed by 2023 IWG response criteria and was defined as complete remission (CR) + CR with bi-lineage blood count recovery (CRbi) + CR with uni-lineage blood count recovery (Cruni) + CR with partial hematological recovery (CRh). Combined clinical and molecular risk was assessed by IPSS-M at times of diagnosis and of HCT, the latter using the bone marrow biopsy and sequencing data collected closest to HCT. High risk was defined as IPSS-M moderately high, high, and very high, whereas low risk was defined as IPSS-M very low, low, and moderately low.

Results: A total of 148 pts with MDS who received HMA and underwent subsequent HCT were included. Median age was 64 years (range 26-79) and 61.5% were men. Pts were diagnosed with MDS-EB1 (26.4%), MDS-EB2 (45.3%), and other MDS subtypes (28.3%). IPSS-M at time of diagnosis was very low (2%), low (10.1%), moderate low (6.1%), moderate high (8.8%), high (31.8%), and very high (22.3%). IPSS-M pre-HCT was very low (12.8%), low (8.8%), moderate low (10.8%), moderate high (12.8%), high (20.3%), and very high (10.8%). IPSS-M at diagnosis and pre-HCT could not be calculated because of missing molecular data in 18.9% and 23.6% of pts, respectively. Pts received a median of 4 HMA cycles (range 1-20) and were treated with azacitidine for 7 days (54.1%), decitabine for 5 days (39.2%), and other schedules (6.7%). Prior to HCT, IWG 2023 responses were: CR (15.5%), CRbi (14.9%), CRuni (19.6%), CRh (0.7%), partial remission (PR: 1.4%), hematological improvement (HI: 9.5%), and no response (38.5%). Most pts received HCT from either a matched unrelated (60.8%) or matched related donor (18.2%) with reduced intensity conditioning (74.3%). Pts received graft versus host disease prophylaxis with tacrolimus (tac)/methotrexate (MTX) (54.7%), tac/MTX/sirolimus (19.6%), post-transplant cyclophosphamide/mycophenolate mofetil/tac (15.5%), tac/sirolimus (8.1%), other (2%). Median HCT-comorbidity index (CI) was 2 (range 0-13) and 48.6% pts had HCT-CI ≥ 3. For the entire cohort, the median follow-up time among ongoing survivors was 48.3 months (range 5.5-101.3). Among pts who responded to HMA per IWG 2023 criteria (CR/CRbi/CRuni/CRh), those who had high risk by IPSS-M prior to HCT had significantly shorter median overall survival (OS) (27 months; 95% CI 7.5-51) compared to pts with a low risk by IPSS-M (not reached; p=0.016) (Figure A). Cumulative incidence of relapse (CIR) at 4 years was 66% for pts with high risk and 31% for low risk (p=0.034) (Figure B). Pts with response to HMA with high risk by IPSS-M had lower OS (4-year OS: 27% versus 53%; p=0.016) and progression-free survival (4-year PFS: 19% versus 50%; p=0.018) but similar non-relapse mortality (NRM) (4-year NRM: 16% vs. 19%; p=0.66) post-HCT compared to pts with low risk at time of HCT.

Conclusion: For pts with MDS who achieve a response to HMA prior to HCT, combined clinical/molecular risk, as assessed by IPSS-M, has an important prognostic impact on post-HCT outcomes. Pre-HCT risk should be evaluated for prognostication and to guide patient care, including future prospective studies evaluating novel agents for post-HCT therapy.

Disclosures: Kelkar: CareDx: Research Funding. Ho: Allovir: Consultancy; Jazz: Consultancy, Research Funding; Omeros: Consultancy; Alexion: Consultancy; CareDx: Research Funding. Koreth: BMS: Research Funding; Clinigen Labs: Consultancy, Research Funding; Amgen: Research Funding; Tr1x: Consultancy; Biolojic Design: Consultancy; Cue Biopharma: Consultancy; Gentibio: Consultancy; Equillium: Consultancy; Mallinckrodt: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Research Funding; Regeneron: Research Funding; Cugene: Membership on an entity's Board of Directors or advisory committees; Equillium: Research Funding. Romee: Biohaven: Research Funding; Inndura: Consultancy. Nikiforow: Sobi: Other: Participation in ad hoc advisory board; Kite/Gilead: Other: Participation in ad hoc advisory board; Iovance: Other: Participation in ad hoc advisory board; GlaxoSmithKline: Other: Participation in ad hoc advisory board; A2 Bio: Other: Participation in ad hoc advisory board. Soiffer: Bluesphere Bio: Consultancy; Astellas: Consultancy; Vor Bipharma: Consultancy; Juno Therapeutics/ BMS/Celgene USA: Other: Data Safety Monitoring Board; NMPD – Be the Match, USA: Membership on an entity's Board of Directors or advisory committees; Smart Immune: Consultancy; Jasper: Consultancy; Neovii: Consultancy. Luskin: Jazz: Honoraria; Pfizer: Honoraria; Novartis: Research Funding; Novartis: Honoraria; AbbVie: Research Funding. Garcia: AbbVie: Consultancy, Research Funding; Pfizer: Research Funding; Prelude: Research Funding; New Wave: Research Funding; AstraZeneca: Research Funding; Servier: Consultancy; Gilead: Consultancy; Astellas: Consultancy; Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy. Chen: Rigel: Consultancy; Abbvie: Consultancy. Lane: AbbVie: Research Funding; Cimeio Therapeutics: Consultancy; IDRx: Consultancy; Jnana Therapeutics: Consultancy; ProeinQure: Consultancy; Qiagen: Consultancy; Medzown: Current equity holder in private company; Stemline Therapeutics: Research Funding. Winer: Curis Inc: Consultancy; Abbvie: Consultancy. Stone: Ligand Pharma: Consultancy; BerGenBio: Consultancy; Cellularity: Consultancy; Syntrix: Other: DSMB; Lava Therapeutics: Consultancy; Takeda: Other: DSMB; Amgen: Consultancy; Jazz: Consultancy; GSK: Consultancy; Rigel: Consultancy; Hermavant: Consultancy; Kura One: Consultancy; AvenCell: Consultancy; Epizyme: Other: DSMB; Aptevo: Other: DSMB; CTI Biopharma: Consultancy; Abbvie: Consultancy. DeAngelo: Incyte: Honoraria; Novartis: Research Funding; Novartis: Honoraria; Kite: Honoraria; Autolus: Honoraria; Takeda: Honoraria; Jazz: Honoraria; Gilead: Honoraria; GlycoMimetics: Research Funding; Blueprint: Honoraria; Pfizer: Honoraria; Servier: Honoraria; AbbVie: Research Funding; Blueprint: Research Funding; Amgen: Honoraria. Zeidan: Gilead: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Tyme: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Orum: Consultancy, Honoraria; Foran: Consultancy, Research Funding; Astex: Research Funding; Geron: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Shattuck Labs: Research Funding; Amgen: Consultancy, Honoraria; Mendus: Consultancy, Honoraria; BioCryst: Consultancy, Honoraria; Zentalis: Consultancy, Honoraria; Ionis: Consultancy, Honoraria; Syros: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; BeyondSpring: Consultancy, Honoraria; Schrödinger: Consultancy, Honoraria; ALX Oncology: Consultancy, Honoraria; Taiho: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Syndax: Consultancy, Honoraria; Kura: Consultancy, Honoraria; Lox Oncology: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Chiesi: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Notable: Consultancy, Honoraria; Genentech: Consultancy, Honoraria. Lindsley: Vertex Pharmaceuticals: Consultancy; Qiagen: Consultancy; Jazz Pharmaceuticals: Consultancy; Verve Therapuetics: Consultancy; Sarepta Therapuetics: Consultancy; Bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Consultancy. Cutler: Sanofi: Consultancy; Cimeio: Membership on an entity's Board of Directors or advisory committees; Oxford Immune Algorithmics: Membership on an entity's Board of Directors or advisory committees; Allovir: Other: Data Safety Monitoring Board (DSMB); Pluristem Therapeutics: Other: DSMB; InhibRx: Consultancy; Astellas: Consultancy; Rigel: Consultancy. Stahl: Kymera: Membership on an entity's Board of Directors or advisory committees; Boston Consulting: Consultancy; Dedham group: Consultancy; Rigel: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: GME activity ; Haymarket Media: Other: GME activity ; Curis Oncology: Other: GME activity ; GSK: Membership on an entity's Board of Directors or advisory committees; Clinical care options: Other: GME activity .

*signifies non-member of ASH