Redefining Allogeneic Transplants & Cellular Therapy: Key Takeaways from EBMT 2025 - Episode 8
Identifying Appropriate Patients for PTCy as GVHD Prophylaxis in AlloHSCT
Panelists discuss how cautious use of posttransplant cyclophosphamide-based (PTCy) graft-vs-host disease (GVHD) prophylaxis may be considered in high-risk patients, certain donor types, or those with toxicity concerns, where more traditional regimens such as calcineurin inhibitors (CNIs) and methotrexate (MTX) may be preferred to balance GVHD prevention and minimize complications.
Summary for Physicians:
In considering GVHD prophylaxis for allogeneic hematopoietic stem cell transplantation, certain patient populations may prompt more cautious use of PTCy in combination with other agents, such as CNIs and MTX.
Key Considerations for Cautious Use of PTCy-Combination:
- High-risk patients with GVHD: In patients with high-risk features, such as those with advanced age, severe comorbidities, or prior history of GVHD, clinicians may prefer to avoid the potential complications associated with PTCy and opt for more traditional regimens such as CNI plusMTX.
- Donor type: For certain donor types, particularly mismatched or haploidentical donors, clinicians may be more cautious with PTCy due to concerns about its effectiveness in preventing GVHD while maintaining a strong graft-vs-leukemia effect. In these cases, the CNI plusMTX combination may be preferred to provide more balanced GVHD prophylaxis.
- Toxicity considerations: Patients with compromised organ function or those at increased risk for infections or nonrelapse mortality may benefit from avoiding PTCy-based regimens due to potential complications, such as nephrotoxicity or myelosuppression, in favor of a CNI plusMTX combination.
In these cases, a more traditional approach with CNI and MTX remains a reasonable option to manage GVHD while minimizing the risk of toxicity in vulnerable patients.
Nelli Bejanyan reports consulting or advisory role for CareDx, Medexus Pharmaceuticals, Orca Biosystems, AlloVir, TScan Therapeutics, and Pfizer; and research funding from CRISPR Therapeutics. Everett Meyer reports sponsored research from Orca Biosciences, Kyverna; and a scientific advisor role and equity holder for GigaMune, Indee, TRACT, Jura Biosciences.Caspian Oliai reports no relevant disclosures (investigator on the Orca T trial funded by Orca Biosciences). Arpita P. Gandhi reports roles with OncLive, MJH Life Sciences, OrcaBio (research), CareDx (Advisory Board). Amandeep Salhotra reports received funding from Rigel, Bristol Myers Squibb and Orca Biosciences; and speakers bureau for Incyte and Sanofi.
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