Introduction to Graft-versus-Host Disease (GVHD)

Summary: Graft versus Host Disease (GVHD) is a common complication after allogeneic stem cell transplant. Learn the difference between acute and chronic GVHD and how each develops. Both standard therapies and exciting new prevention and treatment interventions are discussed.
Presenter: Luke Mountjoy DO, Colorado Blood Cancer Institute, part of Sarah Cannon Cancer Institute at Presbyterian St. Luke's Medical Center
Many thanks to Incyte, Sanofi, and Pharmacyclics an AbbVie Company whose support helped make this Survivorship Symposium possible.
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Highlights:
(03:15): When you receive a stem cell transplant, lymphocytes are infused along with the stem cells. Lymphocytes fight and kill whatever blood cancer you're dealing with, but they also can fight you. They can cause graft-versus-host disease
(07:00): Acute GVHD can occur a few weeks after transplant and usually peaks a few months after transplant and resolves by 1 year. Chronic GVHD can start a few months after transplant, and usually peaks between 1-2 years after transplant. However it can also persist for years.
(10:08): Risk factors for GVHD include the HLA mismatch between patient and donor, a donor who has had multiple pregnancies and older donor age.
(12:15) Clinical features of acute GVHD include skin rash, elevated bilirubin, nausea, vomiting or anorexia and diarrhea. Acute GVHD is graded from 1-4 with 4 being severe symptoms.
(14:44) Chronic GVHD is the most serious and long-term complication of transplant. It occurs in 30-55% of patients. 50% of patients will have 3 or more organs involved. On average, therapy is required for 2-3 years.
(19:31) Transplant success is measured using a GRFS score. This stands for GVHD, relapse-free survival. The goal is to have a successful transplant with no GVHD.
((22:02) Post-transplant Cytoxan® is a new strategy to minimize GVHD. It is a dose of Cytoxan® (Cyclophosphamide) infused on day 3 post-transplant. It works by targeting the T-cells that cause GVHD. In a small study, patients who received post-transplant Cytoxan® were 20% more likely to be alive without relapse and without GVHD at 1 year post-transplant.
(26.21) Clinical trials utilizing ORCA-T are very encouraging. ORCA-T amplifies or increases a patient’s regulatory T-cells which help decrease GVHD. These are then infused back into the patient. Acute GVHD decreased to 5% and chronic GVHD to 6% compared to historical controls. Patients also had improved relapse-free survival and overall survival. Studies are ongoing.
(30:16) The backbone of GVHD therapy is steroids and immunosuppressants. However, the FDA has approved 3 new drugs for the treatment of GVHD including Ibrutinib (Imbruvica®), Ruxolitinib (Jakafi® ) and Belumosudil (Rezurock® ®). These newer medications have been very helpful in managing both acute and chronic GVHD.
(36:55) The prevention and treatment of GVHD are improving at a remarkable rate. There are currently many clinical trials focused on learning more about how we can continue to minimize transplant complications of GVHD while improving outcomes.
April 2024, Part of the Virtual Celebrating a Second Chance at Life Survivorship Symposium 2024
Presentation is 40 minutes long with 19 minutes of Q & A.
Key Points
Acute GVHD is caused by T-cells. These immune cells attack the skin, digestive tract, and liver. Chronic GVHD not only involves T-cell activation but also B-cells. B-cells are immune cells that develop antibodies that deposit in tissues, causing symptoms such as dry eyes and mouth, tightening of the skin and tissues, decreased appetite, and diarrhea.
In the past, the incidence of acute GVHD was 70%. However, with the introduction of new interventions such as post-treatment Cyclophosphamide (Cytoxan® ), graft manipulation, and ORCA-T, the incidence in clinical trials has decreased to 5-6%. This has also led to improved one-year relapse rates and overall survival rates in clinical trials.
There are now new drugs approved for GVHD treatment, including Ibrutinib (Imbruvica®), Ruxolitinib (Jakafi®), and Belomosudil (Rezurock®). Although each drug can have side effects, they are helping improve patients' symptoms and overall quality of life.
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