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1042 Superiority of Post-Transplant Cyclophosphamide-Based Graft Versus Host Disease (GvHD) Prophylaxis in Patients 70 Years and Older: A BMT CTN 1703 Post-Hoc Analysis

Program: Oral and Poster Abstracts
Type: Oral
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Avoiding GVHD and Improving Outcomes
Hematology Disease Topics & Pathways:
Research, Clinical trials, Elderly, Clinical Research, Treatment Considerations, Study Population, Human
Monday, December 9, 2024: 5:15 PM

Sameem Abedin, MD1, Qinghua Lian2*, Michael J Martens, PhD3*, Monzr M. Al Malki, MD4, Hany Elmariah, MD, MS5, Mahasweta Gooptu, MD6, Karilyn T. Larkin, MD7, Brian C. Shaffer, MD, MS8, Alison W Loren, MD9, Melhem M. Solh, MD10, Amin M. Alousi, MD11*, Omer Jamy, MD12, Janny M. Yao, PharmD13*, Kristy Applegate14*, Miguel Angel Perales, MD15, Leslie Kean, MD16, Yvonne A. Efebera, MD17, Ran Reshef, MD, MSc18, William Clark, MD, MS19*, Eric Leifer, PhD20*, Mary M. Horowitz, MD21, Richard J. Jones, MD22, Javier Bolanos-Meade, MD23*, Shernan G. Holtan, MD24 and Mehdi Hamadani, MD25

1Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI
2Medical College of Wisconsin, Milwaukee, WI
3Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI
4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
5Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
6Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA
7Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
8Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
9Abramson Cancer Center, University of Pennsylvania Medical Center, Philadelphia, PA
10BMT Group of Georgia, Atlanta, GA
11Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
12O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, AL
13Pharmacy, City of Hope National Medical Center, Duarte, CA
14Emmes Corporation, Rockville, MD
15Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
16Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA
17Blood and Marrow Transplant and Cellular Therapy Program, OhioHealth, Columbus, OH
18Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
19Virginia Commonwealth University, Richmond, VA
20NHLBI, Bethesda
21Center for International Blood and Marrow Transplant Research (CIBMTR), Minneapolis, MN
22Johns Hopkins University, Baltimore, MD
23Johns Hopkins University Kimmel Cancer Center, Ellicott City, MD
24Department of Medicine, Umn Medical School, Minneapolis, MN
25Department of Medicine, Medical College of Wisconsin, Milwaukee, WI

Introduction

Allogeneic hematopoietic cell transplant (HCT) in adults ≥70 years is increasing with improved donor availability, newer disease therapies, and increasingly preserved fitness. Registry studies indicate that these older patients represent a frailer transplant population overall, with a historical 1-year non-relapse mortality (NRM) at around 25%.

BMT CTN 1703 enrolled adult patients undergoing allogeneic HCT with a matched related donor, or 7-8/8 HLA-matched unrelated donor and reduced intensity conditioning (Bolanos-Meade NEJM, 2023). Patients were randomized 1:1 to post-transplant cyclophosphamide, tacrolimus, and mycophenolate (PTCy/Tac/MMF) or tacrolimus and methotrexate (Tac/MTX) and the primary endpoint was 1-year GVHD/relapse or progression-free survival (GRFS). Overall, a superior 1-year GRFS rate was seen with PTCy/Tac/MMF, however NRM and overall survival (OS) did not differ between treatment arms. We report here, a post hoc analysis of patients ≥70 years randomized on the BMT CTN 1703 protocol.

Methods

Patients ≥70 years randomized on BMT CTN 1703 (PTCy=43, Tac/MTX=53; N=96) were included. The primary endpoint of this post-hoc analysis was 1y-GRFS. Secondary endpoints included infections, engraftment, incidence/severity of acute and chronic GVHD, relapse/progression, adverse events, NRM, and OS in these patients.

Results

Baseline characteristics were balanced between the two treatment arms. Median age at transplant between patients treated with PTCy/Tac/MMF and Tac/MTX was 72 years (70.1-78.6y) and 73 years (70.1-77.4) respectively. In similar order 88% and 85% underwent HCT with HLA matched unrelated donor, and 46% and 40% received Flu/Mel conditioning, which was the most common conditioning regimen. Multivariate Cox model of GRFS revealed that the PTCy/Tac/MMF maintained superiority over Tac/MTX with a significantly lower hazard of GRFS (0.341, 95% CI 0.184-0.633, p<0.001). The adjusted 1-year GRFS rate was 63.1% (95%CI, 47.9%,74.9%) for PTCy and 29.9% (95%CI, 19.2,41.3%) for Tac/MTX. With PTCy/Tac/MMF or Tac/MTX, rates of grade III-IV acute GVHD at Day 100 were 0% and 9.9% (p=0.175), and rates of chronic GVHD requiring immunosuppression were 18.3% and 24.4% (p=0.089). The cumulative incidence of neutrophil recovery (>500mm3) by day 28 was similar between arms (92.8% vs 92.8%, p=0.85). From a toxicity standpoint, with PTCy/Tac/MMF or Tac/MTX, rates of grade 3 infections at 6 months were 4.6% and 11.8%, rates of Grade 3-5 cardiac events were 30.2% and 34%, and rates of Grade 3-5 renal events were 14.0% and 15.1%; none were significantly different. Together, 1-year NRM was significantly lower in PTCy/Tac/MMF treated patients at 4.6% compared to 20.0% with Tac/MTX (p=0.038). Finally, incidence of relapse/progression at 1-year was 19.5% in patients receiving PTCy/Tac/MMF and 25.7% with Tac/MTX (p=0.232). Overall, there was a significant overall survival benefit with PTCy at 1 year post transplant at 90.6% in PTCy/Tac/MMF treated patients compared to 61.8% with Tac/MTX (p=0.003).

Conclusions

This post-hoc analysis of transplant recipients ≥70 years confirms that even in this older, frailer sub-population, PTCy/Tac/MMF is standard of care in patients for GVHD prophylaxis following HLA-matched RIC HCT. The PTCy arm of BMT CTN 1703 showed superior GRFS, lower NRM, and increased OS in in septuagenarians, in whom the apprehension concerning excess toxicity has been greatest.

Disclosures: Abedin: AbbVie, Daichii Sankyo, Servier: Consultancy, Honoraria; Actinium Pharmaceutical, AltruBio, Incyte: Research Funding. Al Malki: Tr1X: Consultancy; Tscan: Consultancy; Stemline therapeutics: Research Funding; CareDx: Consultancy; Incyte: Research Funding; NexImmune: Consultancy, Research Funding. Elmariah: BMS: Research Funding; Shoreline Biosciences: Consultancy. Gooptu: Syndax: Consultancy, Other: Travel expenses. Shaffer: Hansa Biopharma: Consultancy. Solh: GlaxoSmithKline: Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; Sanofi: Consultancy. Perales: Bristol-Myers Squibb: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Research Funding; Vor Biopharma: Consultancy; AbbVie: Honoraria; VectivBio AG: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Syncopation: Consultancy; OrcaBio: Consultancy, Current holder of stock options in a privately-held company; Cidara Therapeutics: Other: DSMB member; Sellas: Other: DSMB member; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Omeros: Consultancy, Current equity holder in publicly-traded company; Sanofi: Consultancy; Incyte: Consultancy, Honoraria, Research Funding; Adicet: Consultancy; Celgene: Consultancy, Honoraria; Allovir: Consultancy; Allogene: Consultancy, Research Funding; Caribou Biosciences: Consultancy; Astellas: Honoraria; Karyopharm: Honoraria; MorphoSys: Honoraria; Takeda: Honoraria; Medigene: Other: DSMB member; Servier: Other: DSMB member. Efebera: Takeda, Janssen, Akcea Therapeutics, Alnylum: Speakers Bureau; Oncopeptides, Sanofi, Janssen Oncology, Pfizer: Consultancy; Takeda, Oncopeptides, Alnylam, Sanofi, GlaxoSmithKline, ORCA Therapeutics, Bristol Myers Squibb/Celgene, Pharmacyclics through Alliance and AFT: Research Funding. Reshef: Orca Bio: Consultancy; Autolus: Consultancy; Sanofi: Research Funding; Atara Biotherapeutics: Research Funding; J&J: Research Funding; Immatics: Research Funding; Quell Biotherapeutics: Consultancy; Takeda: Research Funding; Gilead Sciences: Consultancy, Research Funding; Cabaletta: Research Funding; TCR2: Research Funding; Abbvie: Research Funding; Synthekine: Research Funding; TScan: Consultancy, Research Funding; CareDx: Research Funding; Bayer: Consultancy; Sana Biotechnology: Consultancy; BMS: Research Funding; Incyte: Consultancy, Research Funding; Genentech: Research Funding; Allogene: Consultancy; Precision Biosciences: Research Funding. Clark: Abbvie Inc: Research Funding; Caribou: Consultancy, Research Funding; GPCR Therapeutics, Inc.: Research Funding; IMMPACT Bio: Research Funding; Janssen: Research Funding; Kite: Research Funding; medac Gesellschaft für klinische Spezialpräparate: Research Funding. Horowitz: CSL Behring: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Astellas: Research Funding; Medac: Research Funding; Sanofi: Research Funding; Gamida Cell: Research Funding; Xenikos: Research Funding; Sobi: Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding. Hamadani: AstraZeneca: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; Forte Biosciences: Consultancy; Genentech: Speakers Bureau; Astellas Pharma: Research Funding; Spectrum Pharmaceuticals: Research Funding; Caribou: Consultancy; Takeda: Research Funding; Allovir: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Byondis: Consultancy; CRISPR: Consultancy; DMC, Inc: Speakers Bureau; CRISPR: Speakers Bureau; Autolus: Consultancy; Sanofi Genzyme: Speakers Bureau; Genmab: Consultancy; BMS: Consultancy; Omeros: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau.

*signifies non-member of ASH