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

• Published in: Blood 2024-11, Vol.144, p.1042-1042
• Main Authors: Abedin, Sameem, Lian, Qinghua, Martens, Michael J, Al Malki, MHD Monzr M., Elmariah, Hany, Gooptu, Mahasweta, Larkin, Karilyn T., Shaffer, Brian C., Loren, Alison W, Solh, Melhem M., Alousi, Amin M., Jamy, Omer, Yao, Janny M., Applegate, Kristy, Perales, Miguel Angel, Kean, Leslie, Efebera, Yvonne A., Reshef, Ran, Clark, William, Leifer, Eric, Horowitz, Mary M., Jones, Richard J., Bolanos-Meade, Javier, Holtan, Shernan G., Hamadani, Mehdi
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-193827

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, p500mm3) 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 eve