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4288 Survival Advantage to Allogeneic Transplant in Patients with Myelofibrosis with Intermediate-1 or Higher DIPSS Score

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical: Poster III
Hematology Disease Topics & Pathways:
Diseases, Biological, Therapies, Bone Marrow Failure, transplantation, TKI
Monday, December 3, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Krisstina L. Gowin, DO1, Karen K. Ballen, MD2*, Kwang Woo Ahn, PhD3,4*, Zhen-Huan Hu, MPH3*, Ying Liu, PhD3,5*, Lucia Masarova, MD6*, Srdan Verstovsek, MD, PhD7, Maria Coakley8*, Tania Jain, MBBS9*, Andrew Kuykendall, MD10*, Rami Komrokji, MD11*, Martha Wadleigh, MD12*, Sarah Patches12*, Murat Arcasoy, MD13*, Michael Green13*, Malathi Kandarpa, PhD14*, Moshe Talpaz, MD 15, Haris Ali, MD16, Vikas Gupta, MD, FRCP, FRCPath17, Rebecca Devlin18*, Laura C. Michaelis, MD19, Gabriela S. Hobbs, MD20, Brady Lee Stein, MD21, Ashley Pariser, MD22*, Aaron T. Gerds, MD, MS23, Kierstin Kuber24*, Raajit Rampal25*, Edwin P. Alyea III, MD26, Uday Popat, MD27, Ronald Sobecks, MD28, Bart L Scott, MD29, Ruben Mesa, MD9* and Wael Saber, MD, MS3*

1Department of Hematology, University of Arizona, Tacoma, WA
2Division of hematology/oncology, University of Virginia Health System, Charlottesville, VA
3CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
4Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI
5Division of Biostatistics, Institution for Health and Society, Medical College of Wisconsin, Milwaukee
6Department of Leukemia, UT MD Anderson Cancer Center, Houston, TX
7Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX
8Royal Marsden Hospital, Sutton, United Kingdom
9Mayo Clinic Arizona, Phoenix, AZ
10H. Lee Moffitt Cancer Center, Tampa, FL
11H. Lee Moffitt Cancer Center, Houston, TX
12Dana Farber Cancer Insititute, Boston, MA
13Duke University Medical Center, Durham, NC
14Rogel Cancer Center, The University of Michigan - Michigan Medicine, Ann Arbor, MI
15The University of Michigan Health Systems, Ann Arbor, MI
16Department of Hematology/HCT, City of Hope Medical Center, Duarte, CA
17Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
18Harvard University, Cambridge, MA
19Medical College of Wisconsin, Milwaukee, WI
20Massachusetts General Hospital, Boston, MA
21Dept. of Medicine, Division of Hematology/Oncology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
22Yale Smilow Cancer Center, New Haven, CT
23Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
24Washington University, St. Louis, MO
25Memorial Sloan Kettering Cancer Center, New York, NY
26Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
27Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
28Taussig Cancer Institute, Department of Hematology & Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH
29Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). Consideration of HCT is recommended by international working groups and national guidelines for MF patients (pts) age <70 with intermediate-1 with adverse indicators, intermediate-2 or high-risk disease by the Dynamic International Prognostic Scoring System (DIPSS) for MF– a recommendation made in the absence of clear data indicating the optimal timing of HCT for MF. In this large multicenter retrospective study, we analyze overall survival in MF pts treated with and without HCT.

Methods: Disease characteristics, treatments, and outcome data from MF pts receiving non-transplant therapy at 14 US academic medical centers between 2000-2014 were retrospectively collected. MF pts who underwent HCT were identified from the Center for International Blood and Marrow Transplant Research (CIBMTR). The Cox proportional hazards model was used. The reference time point (time zero) was time of referral for the non-transplant (non-HCT) arm and the time of transplant for the HCT arm. The main effect variable (HCT vs. non-HCT) violated the proportionality assumption where comparing to non-HCT, mortality was higher with HCT in early time period from time zero but then was lower in late time period; therefore, the comparison is presented as early time period and late time period. The Cox model identified 14 months from time zero as the ideal cut point to define early and late time periods. The proportionality assumption is satisfied within each of these two periods.

Results: A total of 1377 and 551 pts were included in the non-HCT and HCT arms, respectively (Table 1). In the overall cohort, survival was higher with non-HCT vs. HCT in early time period (relative risk [RR]: 0.34, P< .0001, Figure 1D), but in late time period survival was lower with non-HCT vs. HCT (RR: 2.37, P< 0.001) (Table 2). In the DIPSS low-risk MF group, while survival was higher with non-HCT vs. HCT in the early time period (RR: 0.19, P=0.007, Figure 1A), survival was lower with non-HCT in the late time period, but the latter did not reach statistical significance (RR: 1.45, P=0.39). In the DIPSS intermediate-1 risk group, a survival advantage was present with non-HCT treatments vs. HCT in the early time period (RR: 0.27, P < .0001, Figure 1B), however survival was lower with non-HCT in the late time period (RR: 3.13, P < .0001). Similarly, in those with DIPSS intermediate-2 and high-risk MF, survival advantage was observed with non-HCT in the early time period (RR: 0.41, P< .0001, Figure IC), but survival was lower with non-HCT in the late time period (RR: 2.82, P < .0001).

Conclusion: A long-term survival advantage with transplant was observed for pts with intermediate-1 or higher risk MF, but at the cost of potential early mortality. The magnitude of benefit increased as DIPSS risk score increased. Although this retrospective study has limitations, the results have an impact on clinical practice by suggesting that transplantation could be considered earlier in the disease course and supports the recommendation for consideration of HCT in the setting of intermediate-1 risk MF.

Disclosures: Gowin: Incyte: Consultancy, Other: Scientific Advisory Board, Speakers Bureau. Verstovsek: Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Consultancy; Italfarmaco: Membership on an entity's Board of Directors or advisory committees. Ali: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding. Michaelis: Incyte: Consultancy; Celgene: Speakers Bureau; Novartis: Consultancy; TG Therapeutics: Consultancy; Jazz Pharmaceuticals: Research Funding. Gerds: Samus Therapeutics: Research Funding; Imago BioSciences: Research Funding; Gnentech: Research Funding; Roche: Research Funding; Celgene: Consultancy, Research Funding; Apexx Oncology: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding.

*signifies non-member of ASH