Patients undergoing stem cell transplants face the risk of developing graft-versus-host disease (GVHD), a condition where donor immune cells attack the recipient's body. The FDA recently approved axatilimab (Niktimvo) for chronic GVHD in patients who have progressed after at least two prior systemic therapies. This approval marks a significant step forward in addressing the challenges of managing this complex condition.
Understanding Chronic GVHD
Chronic GVHD differs significantly from acute GVHD in its pathophysiology and long-term management. While steroids remain the first-line treatment for both acute and chronic GVHD, the approach diverges in subsequent lines of therapy. Ruxolitinib is approved for second-line treatment in both conditions, but further treatments often differ.
Dr. Daniel Wolff, professor at University Hospital Regensburg and an investigator on the AGAVE-201 trial, emphasized that acute GVHD, if not controlled, can be deadly but often resolves. In contrast, chronic GVHD is a long-term condition characterized by significant symptom burden, organ damage, and the need for prolonged immunosuppression. "Chronic GVHD is a chronic disease where you usually don't die, but you are troubled with significant symptom load over a long time with significant treatment side effects and impairment of organs by the disease," Dr. Wolff noted.
Impact on Organ Systems
Acute GVHD primarily affects the skin, gut, and liver, whereas chronic GVHD can impact nearly every organ, including the eyes, oral mucosa, genital mucosa, and lungs. This widespread involvement makes chronic GVHD particularly challenging to manage.
Prevention Strategies and Their Limitations
For nearly three decades, the standard immune suppression regimen involved a calcineurin inhibitor combined with methotrexate or mycophenolate mofetil. This approach, when used with peripheral stem cells, resulted in chronic GVHD rates of 50% to 70%. Newer strategies using anti-thymocyte globulin or post-transplant cyclophosphamide have reduced the incidence to around 30% to 35%.
Graft engineering is an evolving field, with platforms like Orca-T showing promise in further reducing chronic GVHD rates to around 5% to 10%. However, Dr. Wolff cautions against the expectation that chronic GVHD will disappear entirely. He notes that procedures like donor lymphocyte infusions for post-transplant relapse can still induce chronic GVHD, and some patients develop the condition despite new preventive measures. "The idea that chronic GVHD will simply vanish and not occur anymore would be nice, but it's not realistic," he stated.
The Need for Effective Treatments
Despite advances in prevention, effective treatments remain crucial for patients who develop chronic GVHD. The approval of axatilimab offers a new option for those who have failed previous therapies, addressing a critical unmet need in GVHD management. As Dr. Wolff concludes, "GVHD cannot be wholly prevented... We still need effective treatments for those who are affected by the disease."
