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3181 Clinical Factors but Not Somatic Mutations Predict for Survival in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Cell Transplant: Analysis of the North American Myelofibrosis Transplant Outcome (NAMTO) Study

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, adult, Clinical Practice (Health Services and Quality), MPN, Clinical Research, health outcomes research, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Helen Ajufo, MD, MS1, Andriy Derkach, PhD2*, Raajit K. Rampal, MD, PhD1, Christopher Famulare, MS1*, David Nemirovsky, MS2*, Jordan Chervin3*, Vincent Ho, MD4*, Vikas Gupta, MD5, Auro Viswabandya, MD6, H. Joachim Deeg, MD7, Tim Monahan7*, Tania Jain, MD8, Richard J. Jones, MD8, Jeanne Palmer, MD9, Aaron T. Gerds, MD, MS10, Alla Keyzner, MD11, Jonathan Lagdameo12*, Alexandra Gomez-Arteaga, MD13, Koen Van Besien, MD, PhD14, Nikolai A. Podoltsev, MD, PhD15, Christian Puzo16*, Satyajit Kosuri, MD17*, Idoroenyi Amanam, MD18 and Roni Tamari, MD1*

1Memorial Sloan Kettering Cancer Center, New York, NY
2Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
3Weill Cornell, New York, NY
4Dana-Farber Cancer Institute, Boston, MA
5Leukemia Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
6Princess Margaret Cancer Centre, Toronto, Canada
7Fred Hutchinson Cancer Research Center, Seattle, WA
8Johns Hopkins University, Baltimore, MD
9Mayo Clinic - Arizona, Scottsdale, AZ
10Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
11Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York
12Mount Sinai, New York
13NewYork-Presbyterian/Weill Cornell Medicine, New York
14University Hospitals Seidman Cancer Center, Cleveland, OH
15Associate Professor of Medicine, Department of Hematology, Yale School of Medicine, New Haven, CT
16Yale School of Medicine, New Haven, CT
17University of Chicago Medicine, Chicago, IL
18Department of Hematologic Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA

Introduction: Myelofibrosis (MF) is a clonal hematologic malignancy characterized by constitutive JAK-STAT activation and aberrant cytokine signaling. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative therapy in MF. The contribution of disease-, patient- and donor-related factors to allo-HCT outcomes remains to be fully elucidated, as well as the presence of somatic mutations in genes such as ASXL1, EZH2, SRSF2, U2AF1 and IDH1/2 which are associated with worse prognosis in MF patients (pts). In this large multi- center retrospective analysis, we aimed to study the impact of clinical and molecular mutations on transplant outcomes.

Methods: This analysis including 498 pts from 11 centers in North America and Canada. Univariate proportional-hazard Cox regression analysis stratified by center was used to assess the association of patient, transplant, and disease characteristics on overall survival (OS). Baseline patient demographic data and disease characteristics were selected as covariates in the multivariate analysis.

Results: Pts transplanted between 2002-2021 were included in this analysis. Baseline and transplant characteristics are summarized in table 1. The 1- and 2-year OS was 77% (95% CI; 73-81) and 70% (95% CI; 66-74) and non-relapse mortality (NRM) 19% (95% CI: 17-21) and 23% (95% CI: 19-27), respectively. The cumulative incidence (CMI) of relapse at 1- and 2-years was 12% (95% CI; 10-14) and 16% (95% CI; 12-20). The CMI of acute graft versus host disease (aGVHD) grade II-IV was 31% (95% CI; 27-35) at 3 months and 42% (95% CI; 38-46) at 1-year post-transplant and grade was III-IV 13% (95% CI; 11-15) and 18% (95% CI; 14-22), respectively. The CMI of neutrophil engraftment at 1 and 3 months was 90% (95% CI: 87-93) and 97% (95% CI: 95-95) and for platelets 55% (95% CI: 50-59) and 80% (95% CI: 76-83).

Univariate analysis included pts (age and gender), transplant (donor type and conditioning regimen intensity) and disease characteristics (DIPSS, mutations, cytogenetics (CG), blood counts, and spleen size). Hemoglobin > 10 g/dL (HR .5, 95% CI .34 -.73 p=3 x 10-4) and platelets >50× 109/L (HR .59, 95% CI .42-.81, p=.0013) prior to transplant were associated with improved OS. High risk DIPSS was associated with decreased OS (p=0.0002). Mutations in ASXL1, EZH2, IDH1/2, U2AF1 and SRSF2 were not associated with decreased OS in this analysis (Figure 1). However, mutations in ZRSR2 were associated with inferior OS (HR 2.07, 95% CI 1.08-3.95, p=.0252). Lastly, JAK2, which had the most frequent mutations was not associated with OS (HR .0.93, 95% CI .65-1.31). There was no association between the CG risk groups and OS.

Splenomegaly, measured radiographically, had no impact on OS but was strongly associated with engraftment (better engraftment defined as HR>1). For platelets, spleen size of 15.6-18.9 cm HR of 0.69 (95% CI .47-1, p=.0489) and size >18.9-22.5 cm HR of 0.48 ( 95% CI .33-.7, p=1x10^-4). For neutrophils, spleen size >19.9-22.5 cm had a HR of 0.68, (95% CI .48-.96, p=.0268) and size>22.5 cm had a HR of 0.65 (95% CI .46-.91, p=.0114). Mismatched unrelated (MMURD) and haplo identical donors had no impact on survival but were associated with delayed platelet engraftment; MMURD (HR .67, 95% CI .47-.96, p=.0298) and haploidentical donors (HR .56, 95% CI .39-.8, p=.0017). In a multivariate analysis adjusted for age, gender, highest DIPSS, donor type and conditioning regimen, platelets > 50× 109/L (HR .61, 95% CI .44-.87, p=.0053) hemoglobin >10 g/dL (HR .6, 95% CI .4-.9, p=.0244) and lower DIPSS at the time of transplant were associated with improved OS.

Conclusions: In this large multicenter analysis only clinical variables; hemoglobin and platelets, were found to be associated with OS after allo-HCT in MF patients. Somatic mutations associated with poor prognosis were not associated with OS suggesting that transplant can overcome their negative impact. Splenomegaly was associated with delayed engraftment but not OS. Interestingly, using alternative donors (MMURD and haplo identical) didn’t have a negative effect on OS, possibly reflecting the use of post-transplant cyclophosphamide for GVHD prophylaxis in recent years. These results highlight the importance of biologic factors in the prognostication of outcomes in MF pts undergoing allo-HCT independent of somatic mutations.

Supported by the American Society of Hematology (ASH) and MPN Research Foundation

Disclosures: Rampal: Morphosys/Constellation: Consultancy; Servier: Consultancy; Celgene-BMS: Consultancy; CTI BioPharma Corp: Consultancy; Zentalis: Consultancy; GSK-Sierra: Consultancy; Incyte: Research Funding; Zentalis: Research Funding; Constellation: Research Funding; Galecto: Consultancy; Karyopharm: Consultancy; Dainippon: Consultancy; Sumitomo: Consultancy; Ryvu: Research Funding; Pharmaessentia: Consultancy; Stemline: Research Funding; Kartos: Consultancy; Incyte: Consultancy. Ho: Orca Bio: Consultancy; Omeros: Consultancy; Allovir: Consultancy; Alexion, AstraZeneca Rare Disease: Consultancy; CareDx: Research Funding; Jazz Pharmaceuticals: Research Funding; Omeros: Research Funding; Alexion, AstraZeneca Rare Disease: Speakers Bureau. Gupta: BMS, Celgene, Roche, Abb Vie, Pfizer, Sierra Oncology, CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis, BMS Celgene, GSK: Honoraria; Novartis, BMS Celgene, Sierra Oncology, AbbVie, Constellation Biopharma, Pfizer, GSK Pharma, CTI Biopharma: Consultancy; Novartis, BMS Celgene, SMP Oncology, AbbVie, Constellation Biopharma, Pfizer, GSK Pharma, CTI Biopharma: Consultancy; BMS Celgene, Roche, AbbVie, Pfizer, Sierra Oncology, CTI Biopharma, GSK: Other: Participation on a Data Safety Monitoring Board or Advisory Board; GSK: Other: Travel to EHA 2023 for invited talk at GSK sponsored MPN education session . Deeg: CSL Behring: Research Funding. Jain: CTI Biopharma, Kartos therapeutics, Incyte: Research Funding; Care Dx, Bristol Myers Squibb, Incyte, Abbvie, CTI, Kite, Cogent Biosciences, Blueprint Medicine, Telios pharma, Protagonist therapeutics: Membership on an entity's Board of Directors or advisory committees. Palmer: CTI BioPharma Corp.: Consultancy, Honoraria, Other: Money went to institution; morphosys: Consultancy, Other: Money went to institution; Jubliant: Consultancy; Incyte: Consultancy, Other: Money went to the institution; Sierra Oncology: Consultancy, Other: Money went to Institution. Gerds: Accurate Pharmaceuticals, Constellation Pharmaceuticals, CTI BioPharma, Imago BioSciences, Incyte Corporation, Kratos Pharmaceuticals: Research Funding; AbbVie, Bristol Myers Squibb, Constellation Pharmaceuticals, GlaxoSmithKline, Kartos, Novartis, PharmaEssentia, Sierra Oncology: Consultancy. Van Besien: Intellia: Consultancy; Precision Biosciences: Research Funding; Orca: Research Funding; Avertix: Current equity holder in private company; Calibr: Research Funding; BMS: Research Funding; Actinium: Research Funding; Moprhosys: Consultancy; Hemogenyx: Consultancy, Current equity holder in publicly-traded company; SNIPR: Consultancy; Incyte: Consultancy. Podoltsev: Cogent Biosciences: Other: IDMC Member; AI Therapeutics; Arog Pharmaceuticals; Astellas Pharma, Inc.; Astex Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; CTI BioPharma Corp.; Daiichi Sankyo, Inc.; Genentech, Inc.; Jazz Pharmaceuticals, Inc.; Kartos Therapeuti: Research Funding; AbbVie Inc.; Blueprint Medicines (former); Constellation Pharmaceuticals (former); CTI BioPharma Corp. (former); Incyte Corporation (former); Novartis (former); PharmaEssentia (former): Consultancy.

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