Evolving GVHD Prophylaxis: Emerging Drug and Graft Engineering Strategies

Summary for Physicians:

The discussion around advancing outcomes in GVHD management includes various innovative strategies, both in drug development and graft engineering, aimed at improving GVHD prevention and treatment.

Key Strategies to Advance GVHD Outcomes:

• Targeted therapies: New drug development focuses on targeting specific immune pathways involved in GVHD. Agents that block T-cell activation, such as Janus kinase inhibitors and selective inhibitors of costimulatory signaling, are showing promise in reducing GVHD severity while preserving the graft-vs-leukemia effect.
• Cell-based therapies: Graft engineering approaches, such as the use of regulatory T cells (Tregs), are being explored to modulate the immune response and prevent GVHD. Expanding or infusing Tregs from the donor or recipient may help balance immune tolerance and reduce GVHD risk.
• PTCy optimization: While PTCy has proven effective, ongoing research aims to refine its use, including identifying optimal dosing regimens and combining it with novel agents to enhance its ability to prevent GVHD without compromising graft-vs-leukemia activity.
• Biomarkers and early detection: Research into biomarkers for early detection of GVHD or identifying patients at high risk of developing GVHD could enable more personalized approaches, allowing for early intervention and tailored therapies.

These emerging strategies are expected to offer more effective and targeted ways to prevent and treat GVHD, improving long-term outcomes for patients undergoing allogeneic stem cell transplantation.

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.