Dr. Cutler on Treatment Options for Acute and Chronic GVHD

Corey S. Cutler, MD, MPH, FRCPC, medical director, Adult Stem Cell Transplantation Program, director of clinical research, Stem Cell Transplantation, director, Stem Cell Transplantation Survivorship Program, institute physician, Dana-Farber Cancer Institute, and associate professor of medicine, Harvard Medical School, discusses treatment options for patients with acute and chronic graft-versus-host disease (GVHD).

The standard treatment for patients who develop acute GVHD is corticosteroids. These drugs can induce a response rate of 50% to 75%, says Cutler.

In May 2019, the FDA approved ruxolitinib (Jakafi) for the treatment of adult and pediatric patients ≥12 years of age with steroid-refractory acute GVHD. The approval was based on data from the phase II REACH1 trial, in which ruxolitinib led to a 57% overall response rate (ORR). Other agents that may have utility after ruxolitinib are currently under investigation, explains Cutler.

Corticosteroids are the mainstay of treatment in chronic GVHD as well. However, 50% to 60% of patients with chronic GVHD become resistant to corticosteroids within the first year of therapy, says Cutler.

In those cases, ibrutinib (Imbruvica) can be considered. The BTK inhibitor was approved in August 2017 for the treatment of patients with chronic GVHD who progressed on ≥1 line of systemic therapy. The approval was based on data from the single-arm phase Ib/II PCYC-1129 trial, in which ibrutinib led to a 67% ORR.

There is no approved standard third-line therapy for patients with chronic GVHD, says Cutler. However, KD025, an experimental ROCK2 inhibitor, has shown encouraging data in this space. In the phase II ROCKstar trial (NCT03640481), KD025 led to a 64% ORR at a daily dose of 200mg in patients with chronic GVHD who received ≥2 prior systemic therapies.