Video
An Overview of Treatment Options for Chronic GVHD
Author(s):
A comprehensive review of the treatment armamentarium for patients with chronic graft vs host disease.
Transcript:
Corey Cutler, MD, MPH, FRCPC: Acute and chronic graft versus host disease [GVHD] are managed very similarly, at least in the upfront setting, where corticosteroids really are the mainstay of treatment. In the chronic GVHD setting, we have tried to add additional agents to the initial therapy. Most recently, we tried in a very large trial to add the Bruton tyrosine kinase [BTK] inhibitor ibrutinib to corticosteroids as upfront therapy in chronic graft versus host disease. Unfortunately, that trial did not pan out. While there was some evidence that curves were splitting later on, it did not appear to add much in the early time points after the initiation of therapy. So, initial therapy of chronic GVHD actually remains corticosteroids. Some individuals add drugs like tacrolimus. More recently, a CTN [Clinical Trials Network] study suggested that sirolimus might be more effective as a frontline therapy when added to corticosteroids.
Beyond frontline therapy for chronic graft versus host disease, there are a number of different options. Ibrutinib, the BTK inhibitor, is actually approved as a second-line therapy in chronic GVHD. Very recently, ruxolitinib, the JAK inhibitor, was approved in a similar setting. Beyond that, belumosudil or KD025, has recently been approved for individuals with steroid-refractory chronic GVHD who have progressed despite 2 lines of therapy. After that, there are a number of drugs that are regularly used that do not actually have FDA labels but are considered standard of care. Lots of people use extracorporeal phototherapy. There’s still a lot of use of things like rituximab or other monoclonal antibodies. Some people still use mycophenolate despite some evidence against its efficacy. There really are a lot of options that we have, although now there are 3 FDA-indicated drugs in this setting.
There are a lot of different definitions of steroid-refractory chronic graft versus host disease. In acute GVHD, we have some very clear definitions, and those have been accepted widely throughout the community. In chronic GVHD, the definitions are a little less widely accepted. Each of the trials that have led to the approval of an agent in chronic GVHD used separate criteria. In my hands, steroid-refractory chronic GVHD refers to someone who is progressing despite several weeks of corticosteroids at a dose of approximately 1 mg/kg/day. There are some patients who are steroid-dependent, and these are people in whom you cannot taper corticosteroids below a reasonable dose before chronic GVHD flares. Those people are generally eligible for second-line therapy and beyond. There are some people who simply do not get an adequate response to corticosteroids despite at least 1 month of therapy, and those people can be considered steroid-refractory as well. All of these definitions are a little bit user-dependent and have been defined slightly differently depending on the nature of the clinical trial in which they’re being applied.
Transcript edited for clarity.
