Impact of posttransplant cyclophosphamide-based GVHD prophylaxis in patients 70 years and older: an update from BMT CTN 1703

Blood Adv. 2025 Jul 22;9(14):3495-3501. doi: 10.1182/bloodadvances.2025015964.

Abstract

Allogeneic hematopoietic cell transplant (allo-HCT) is underutilized in adults aged ≥70 years. Morbidity, often driven by graft-versus-host disease (GVHD), is considered a major barrier to its use. The BMT CTN 1703 trial (ClinicalTrials.gov identifier: NCT03959241) randomly assigned adults with hematologic malignancies undergoing allo-HCT after reduced intensity conditioning to receive either posttransplant cyclophosphamide, mycophenolate mofetil, and tacrolimus (PTCy) or tacrolimus and methotrexate (Tac/MTX) for GVHD prophylaxis. Overall study results revealed superior GVHD-free, relapse-free survival (GRFS) with PTCy-based prophylaxis. This analysis explored the impact of PTCy in patients aged ≥70 years enrolled in BMT CTN 1703. We analyzed outcomes for 96 patients aged ≥70 years. PTCy maintained superiority for the primary end point with a GRFS rate of 67.1% compared with 29.5% with Tac/MTX (P = .001). GVHD control and improved immunosuppression-free survival contributed to a lower 1-year nonrelapse mortality (NRM) with PTCy. Furthermore, lower rates of relapse/progression were observed with PTCy, altogether resulting in significantly improved adjusted 1-year survival with PTCy at 94.3% vs 60.2% with Tac/MTX (P = .001). PTCy-based GVHD prophylaxis should be considered standard prophylaxis for older adults. Given low rates of NRM and excellent survival outcomes with this approach, there should be greater consideration for allo-HCT in older patients, particularly patients aged ≥70 years. This trial was registered at www.ClinicalTrials.gov as #NCT03959241.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / therapeutic use
  • Female
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / prevention & control
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Male
  • Methotrexate / therapeutic use
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Cyclophosphamide
  • Immunosuppressive Agents
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT03959241