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897 Patient-Reported Outcomes of BMT CTN 1703: A Randomized Phase III Study for Gvhd Prophylaxis - a Quality of Life Evaluation

Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Modern Challenges in Transplantation
Hematology Disease Topics & Pathways:
clinical trials, Research, adult, health outcomes research, Clinical Research, Study Population, Human
Monday, December 11, 2023: 3:15 PM

Shernan G. Holtan, MD1, Michael J Martens, PhD2*, Monzr M. Al Malki, MD3, Yvonne Adeduni Efebera, MD, MPH4, Carrie L. Kitko, MD5, Ran Reshef, MD, MSc6, Andrew R. Rezvani, MD, BA7*, Brian C. Shaffer, MD8, Melhem M. Solh, MD9, Janny M. Yao, PharmD10*, Lyndsey Runaas, MD11*, Hany Elmariah, MD, MS12, Karilyn T. Larkin, MD13, Najla El Jurdi, MD14, Mahasweta Gooptu, MD15, Alison W Loren, MD16, Aric C. Hall, MD17*, Amin Alousi18*, Omer Jamy, MD19, William Clark, MD, MS20*, Leslie Kean21, Ami S. Bhatt22, Miguel-Angel Perales, MD23, Kristy Applegate24*, Juan WU25*, Eric Liefer26*, Nancy DiFronzo, PhD27*, Richard J. Jones, MD28, Mary M. Horowitz, MD29, Deborah Mattila, BA30*, Mehdi Hamadani, MD31 and Javier Bolanos-Meade, MD, KHS32*

1Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN
2Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI
3Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
4Division of Blood and Marrow Transplant and Cellular Therapy, OhioHealth, Columbus, OH
5Division of Pediatric Hematology/Oncology, Department of Pediatrics, Vanderbilt University, Nashville, TN
6Division of Hematology & Oncology, Columbia University Medical Center, New York
7Stanford University Cancer Institute, Palo Alto, CA
8Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
9BMT Group of Georgia, Atlanta, GA
10Pharmacy, City of Hope National Medical Center, Duarte, CA
11Medical College of Wisconsin, Milwaukee, WI
12Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
13Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
14Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, minneapolis, MN
15Medical Oncology, Dana-Farber Cancer Institute, Brookline, MA
16Cellular Therapy and Transplantation, Perelman Center for Advanced Medicine, Philadelphia, PA
17Division of Hematology/Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
18Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
19Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
20Virginia Commonwealth University, Richmond, VA
21Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA
22Stanford University, Stanford, CA
23Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
24Emmes Corporation, Rockville, MD
25The EMMES Corporation, Rockville, MD
26National Institutes of Health, Bethesda
27Division of Blood Diseases & Resources, The National Heart, Lung, and Blood Institute, Bethesda, MD
28Johns Hopkins University, Baltimore, MD
29Center for International Blood and Marrow Transplant Research, Milwaukee, WI
30National Marrow Donor Program/Be The Match, Center for International Blood and Marrow Transplant Research, Minneapolis, MN
31Division of Hematology and Oncology, The Medical College of Wisconsin Inc, Milwaukee, WI
32Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD


A randomized phase III trial of post-transplantation cyclophosphamide (PTCy), tacrolimus, (Tac), and mycophenolate mofetil (MMF) versus tacrolimus/methotrexate (Tac/MTX) for graft-versus-host disease (GVHD) prophylaxis showed superior graft-versus-host disease-free, relapse-free survival (GRFS) in the PTCy-containing arm (NEJM, 2023). Here, we report the effect of GVHD prophylaxis on patient-reported outcomes and impact on quality of life (QOL).


The QOL study component of BMT CTN 1703 employed four primary endpoints: Lee Chronic GVHD Symptom Score and the PROMIS subscales of physical function, gastrointestinal symptoms, and satisfaction with participation in social roles. Secondary endpoints included hemorrhagic cystitis symptoms and Lee symptom subscale differences, with questionnaires to English and Spanish-speaking participants at enrollment and on Days 100, 180, and 365 post-transplant. Given the risk of missing assessments, an inverse probability weighted–independent estimating equations (IPW-IEE) model was applied for score comparison between arms, adjusting for baseline score, assessment time, age, donor type, disease risk index (DRI), planned conditioning regimen, and planned use of post-transplant maintenance therapy. Significance was declared at a 1.25% level for score comparisons between arms after Bonferroni correction for multiple testing. The analysis approach classified patients according to the intention-to-treat principle.


QOL survey completion rates for patients at each timepoint were similar, exceeding 70% in each study arm. With the Lee Chronic GVHD Symptom Scale, higher scores indicate more severe symptoms. The IPW-IEE models indicated that the Lee Chronic GVHD Symptom Scale total scores were significantly lower in the PTCy arm compared to Tac/MTX at day 100 (mean difference [MD] -2.22, 99% confidence interval [CI] -5.05 to 0.61) and day 365 (MD -1.84, 99% CI -5.13 to 1.45, p=0.01 for overall treatment effect across all timepoints, Figure 1). Nutrition subscores were significantly better with PTCy at day 100 (MD -2.41, 99% CI -5.06 to 0.24, p=0.0014). Mouth scores were significantly better in the PTCy arm at day 365 (MD -7.09, 99% CI -13.21 to -0.98, p=0.0035). Patients over 65 years of age had better psychological subscores across the study population (MD -4.80, 99% CI -8.91 to -0.69, p=0.0026); no interaction was found between age and study treatment. Patient-reported hemorrhagic cystitis symptoms showed no significant difference between the study arms at any post-transplant time point. There was no significant treatment effect observed on the 3 PROMIS subscales. Across the entire study population, both relapse and acute GVHD were associated with worse scores on the Lee Symptom Scale, and PROMIS physical function, gastrointestinal symptoms, and social functions subscales. Chronic GVHD was associated with worse scores on the Lee Symptom Scale only, not the PROMIS subscales. No associations were found between patient-reported QOL at baseline and 1-year GRFS, disease-free survival, or overall survival.


The PTCy arm of BMT CTN 1703 showed superior GRFS, and this study confirms better patient-reported outcomes with PTCy. Patients who received PTCy showed better nutrition and mouth subscores on the Lee Chronic GVHD Symptom Scale compared to those who received Tac/MTX, possibly due to lower observed rates of severe acute and chronic GVHD in the PTCy arm. No association was found between patient-reported baseline quality of life and survival endpoints, suggesting the necessity of further research to elucidate the interplay of treatment strategies, patient factors, and their impact on long-term outcomes.

Disclosures: Holtan: Incyte: Research Funding; Sanofi: Research Funding; Ossium: Consultancy; Vitrac: Research Funding; CSL Behring: Other: Endpoint Adjudication Committee. Al Malki: Tscan: Consultancy. Efebera: Pfizer: Honoraria, Speakers Bureau; Adaptive: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; orca: Other: Chair adjudicatiion committee; Takeda: Other: Chair adjudication Committee; Janssen: Honoraria, Speakers Bureau. Kitko: Horizon: Membership on an entity's Board of Directors or advisory committees. Reshef: TScan Therapeutics: Consultancy. Rezvani: Pharmacyclics.: Research Funding. Shaffer: Hansa Biopharma: Consultancy; Gamida Cell: Consultancy, Research Funding. Solh: Bristol-Myers Squibb: Speakers Bureau. Elmariah: Bristol Myers Squibb: Research Funding. Larkin: Gilead: Honoraria; Debiopharm international: Research Funding; Astellas Pharma: Consultancy. Jamy: Ascentage: Other: Advisory Board Participation. Kean: Tessera: Research Funding; Vertex: Consultancy, Membership on an entity's Board of Directors or advisory committees; HiFiBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers squibb: Patents & Royalties: royalties for clinical trial results., Research Funding; Mammoth: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Merck EMD Serono: Research Funding; Vor: Other: Materials Transfer Agreement; Regeneron: Research Funding; Gilead: Research Funding. Perales: Allogene: Research Funding; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Servier: Other; NexImmune: Consultancy, Current equity holder in publicly-traded company; Medigene: Consultancy, Other; Adicet: Honoraria; Celgene: Honoraria; Syncopation: Honoraria; Cidara Therapeutics: Consultancy, Other; Vor Biopharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Omeros: Consultancy, Current equity holder in publicly-traded company, Honoraria; Miltenyi Biotec: Honoraria; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Orcabio: Consultancy, Current equity holder in publicly-traded company, Honoraria; Allovir: Consultancy; AbbVie: Consultancy, Honoraria; Exevir: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria, Research Funding; VectivBio AG: Consultancy, Honoraria; DSMB: Other; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Caribou: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Equillium: Consultancy, Honoraria; Sellas Life Sciences: Consultancy. Hamadani: Takeda: Research Funding; Genentech: Honoraria; Genmab: Consultancy; Legend Biotech: Consultancy; Kadmon: Consultancy; SeaGen: Consultancy; Novartis: Consultancy; MorphoSys: Consultancy; Incyte: Consultancy; Gamida Cell: Consultancy; BeiGene: Speakers Bureau; Kite, a Gilead Company: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Caribou: Consultancy; Bristol Myers Squibb: Consultancy; Genmab: Consultancy; CRISPR: Consultancy; Omeros: Consultancy; Abbvie: Consultancy; ADC therapeutics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Myeloid Therapeutics: Honoraria; Astra Zeneca: Speakers Bureau; Sanofi Genzyme: Speakers Bureau; BeiGene: Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; Astellas: Research Funding.

*signifies non-member of ASH