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4978 Impact of Clinical and Genetic Factors on Myelofibrosis Outcomes after Allogeneic Transplantation

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Technology and Procedures, molecular testing
Monday, December 11, 2023, 6:00 PM-8:00 PM

Mahasweta Gooptu, MD1, Haesook T. Kim, PhD2, Kaina Chen1*, Ann Mullally, MD3, Joseph Antin, MD1*, Corey Cutler1, Amar H Kelkar, MD1, John Koreth, MD, MBBS, PhD, DPhil1, Roman M. Shapiro, MD1, Robert J. Soiffer, MD1, Daniel J. DeAngelo4, Jacqueline S. Garcia, MD5, Marlise R. Luskin, MD4, Richard M Stone, MD1, Martha Wadleigh, MD1, Eric S. Winer, MD1, R. Coleman Lindsley6 and Vincent Ho, MD1*

1Dana-Farber Cancer Institute, Boston, MA
2Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
3Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA
4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
5Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
6Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA


The reported impact of gene mutations, including JAK2-V617F, other MPN phenotypic drivers and additional cooccurring mutations on outcomes after allogeneic transplantation (HCT) in myelofibrosis (MF) has been inconsistent. While the MTSS score incorporated ASXL1 and JAK2 (non MPL/CALR mutations) as unfavorable predictors after HCT, other studies reported JAK2 mutations to be favorable (Blood 2010). Further, in some studies, mutations known to affect disease progression in MF pre-HCT (high-molecular risk or HMR mutations) have not been predictors of post-HCT outcomes. Here we present outcomes in all MF patients undergoing HCT at Dana-Farber Cancer Institute (DFCI) from 2000-2020 and examine clinical and genetic predictors of outcomes, stratified by year of HCT (<2011 or pre-2011 and >2011 or post-2011). Of note, ruxolitinib was available for use post-2011 only, following its FDA approval that year.


Patients with MF who underwent HCT from 2000-2020 at DFCI (n=166) were included in this retrospective cohort analysis. Outcomes were analyzed for the whole cohort as well as sub-group analyses in the pre-2011 (n=39) and post-2011 era (n=127). Mutational analysis was performed by targeted next-generation sequencing of available pre-HCT samples in 115/127 patients in the post-2011 era.


Median age was 61 years and follow up 56.2 months. 25% had massive splenomegaly. DIPSS-plus scores were high in 45.2% and 45.1% received rux. HCT and patient characteristics (including KPS and median time from diagnosis to HCT) were similar pre and post 2011, with differences in conditioning regimens. Majority (77.1%) had HLA-matched donors, underwent reduced intensity (69.3%) HCT with peripheral blood stem-cells (92.2%) and received tacrolimus/methotrexate based GVHD prophylaxis (90.1%). FluMel100/140 (n=65), FluBu4 (n=34) and FluBu2 (n=11) were commonly used in the post-2011 era, while Flu/Bu1 (n= 34), ablative Bu/Cy (n=5) and Cy/TBI (n=12) were predominant pre-2011. Few patients underwent pre-HCT splenectomy (10.2%) or splenic irradiation (9%). Median D100 donor chimerism was 68% for Flu/Bu1, 86% for Flu/Bu2, 98% for Flu/Bu4, and 100% for Flu/Mel100-140.

At 4 years, overall survival (OS) for the whole cohort was 58% (50,66), progression-free survival (PFS) 55% (47,63), non-relapse mortality (NRM) 23% (17,30) and relapse rate 21%. 4 year OS was significantly better in the post-2011 era compared to pre-2011 (69% vs 26%, p<0.0001), as was PFS, driven by lower relapse rates in the post-2011 era (15% vs 41%, p<0.0001). 4-yr NRM was also marginally better (20% vs 33%, p= 0.17).

In the post-2011 era, 115/127 patients had NGS panel-based genetic analysis prior to HCT (Fig 1), demonstrating 91.3% of patients had at least one driver mutation (JAK2 62.6%, CAL-R 13.9%, MPL 14.8%) while 8.7% patients were triple negative. The most frequent cooccurring mutations were ASXL1 (40%), TET2 (28.7%) and U2AF1 (17.4%). In univariable analysis (UVA), the presence of JAK2 mutations (JAK2+) was associated with superior PFS (HR 0.5, 95% CI 0.27,0.94, p= 0.03) while CALR (HR 1.86, p=0.12) and MPL (HR:1.21, p=0.65) mutations were not significant for PFS. Triple negative patients showed a trend towards poorer PFS (HR 2.27, p=0.05). OS results mirrored those of PFS. No cooccurring myeloid gene mutations were associated with PFS or OS. Superior 4-year OS for JAK2+ versus JAK2- recipients (80% versus 58%, p=0.01) is shown in Figure 2. TP53 (p=0.03), TET2 (p=0.015) and EZH2 (p=0.002) mutations were associated with higher relapse rates in UVA. Patients with JAK2+ and cooccurring ASXL1 mutations had poorer OS compared to those with JAK2+/no cooccurring ASXL1 mutations (HR=2.69, p=0.031).

Combining clinical and molecular features in the post-2011 era, in MVA, only DIPSS high (HR=4.76, p=0.03) and KPS < 90% (HR=2.66, p=0.024) were significantly associated with poorer OS/PFS while JAK2+ (HR=0.32, 95% CI 0.14,0.75,p=0.009) was significantly associated with better OS/PFS; JAK inhibitor use, spleen size/management, conditioning regimen or other mutations including HMR mutations and TP53 were not significantly associated with OS/PFS.


In this single-institution retrospective analysis, the presence of a JAK2-V617F mutation was associated with better OS and PFS following HCT in MF in the post-2011 era. Survival outcomes are significantly better in the post-2011 era compared to pre-2011, in our cohort.

Disclosures: Mullally: Aclaris, Cellarity, Morphic, Biomarin: Consultancy; Constellation, Protagonist: Other: Advisory Board ; AOP Health: Speakers Bureau; Relay, Morphic: Research Funding; PharmaEssentia, Incyte: Other: Steering Committee . Cutler: Oxford Immune Algorithmics: Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy; Sanofi: Consultancy; Cimeio: 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. Kelkar: CareDx: Research Funding. Koreth: Mallinckrodt: Membership on an entity's Board of Directors or advisory committees; Equillium: Consultancy; Gentibio: Consultancy; Cue Biopharma: Consultancy; Biolojic Design: Consultancy; Tr1x: Consultancy; Amgen: Research Funding; Clinigen Labs: Consultancy, Research Funding; BMS: Research Funding; Miltenyi Biotec: Research Funding; Regeneron: Research Funding; Equillium: Research Funding; Cugene: Membership on an entity's Board of Directors or advisory committees. Soiffer: Neovii: Consultancy; Bluesphere Bio: Consultancy; NMPD – Be the Match, USA: Membership on an entity's Board of Directors or advisory committees; Jasper: Consultancy; Juno Therapeutics/ BMS/Celgene USA: Other: Data Safety Monitoring Board; Smart Immune: Consultancy; Vor Bipharma: Consultancy; Astellas: Consultancy. DeAngelo: Servier: Honoraria; Amgen: Honoraria; Autolus: Honoraria; Takeda: Honoraria; Gilead: Honoraria; Novartis: Research Funding; Blueprint: Research Funding; AbbVie: Research Funding; GlycoMimetics: Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Kite: Honoraria; Incyte: Honoraria; Blueprint: Honoraria; Jazz: Honoraria. Garcia: Bristol Myers Squibb: Consultancy; Astellas: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Research Funding; New Wave: Research Funding; AstraZeneca: Research Funding; Pfizer: Research Funding; Prelude: Research Funding; AbbVie: Consultancy, Research Funding; Servier: Consultancy. Luskin: Jazz: Honoraria; Pfizer: Honoraria; Novartis: Research Funding; Novartis: Honoraria; AbbVie: Research Funding. Stone: Rigel: Consultancy; Ligand Pharma: Consultancy; AvenCell: Consultancy; Takeda: Other: DSMB; Amgen: Consultancy; Syntrix: Other: DSMB; Kura One: Consultancy; Cellularity: Consultancy; BerGenBio: Consultancy; Jazz: Consultancy; Lava Therapeutics: Consultancy; Hermavant: Consultancy; GSK: Consultancy; Epizyme: Other: DSMB; Aptevo: Other: DSMB; CTI Biopharma: Consultancy; Abbvie: Consultancy. Winer: Curis Inc: Consultancy; Abbvie: Consultancy. Lindsley: Vertex Pharmaceuticals: Consultancy; Verve Therapuetics: Consultancy; Jazz Pharmaceuticals: Consultancy; Bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Qiagen: Consultancy; Sarepta Therapuetics: Consultancy; Takeda Pharmaceuticals: 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.

*signifies non-member of ASH