Chronic graft-versus-host disease (GVHD) is a severe adverse reaction after allogeneic hematopoietic cell transplantation that decreases quality of life and is a major cause of death. In July 2021, the U.S. Food and Drug Administration approved belumosudil (RezurockTM) as a third-line treatment option for chronic GVHD.
Kinase inhibitor/selective ROCK2 inhibitor
Mechanism of Action
Belumosudil inhibits rho-associated, coiled-coil containing protein kinase 2 (ROCK2) by downregulating STAT3’s proinflammatory response. The action leads to decreased type 17 and T follicular helper cells, which creates increased regulatory T cells via upregulation of STAT5.
Treatment of patients aged 12 and older with chronic GVHD following failure of at least two lines of systemic therapy
200 mg once daily until chronic GVHD progression, or 200 mg twice daily if taken concurrent with a strong CYP3A inducer or a proton pump inhibitor daily
Take one 200 mg tablet orally with food once a day. Tablets cannot be crushed, cut, or chewed and should be taken at approximately the same time each day. Missed doses can be taken as soon as possible on the same day, then return to the regular schedule on the following day. Do not take an extra dose if it was missed on the prior day.
More than 20% of patients in the drug’s clinical trials experienced infection, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, and hypertension. Abnormal laboratory values included decreased phosphate or lymphocytes and decreased gamma glutamyl transferase. In the clinical trials, 12%–18% of patients discontinued belumosudil because of toxicity.
Because of a risk for hepatotoxicity, monitor hepatic function monthly, including total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. Dose adjustments may be needed for grade 2 or higher hepatotoxicity. Verify pregnancy status before initiating treatment in females of reproductive potential. Conduct a complete medication reconciliation that includes any prescriptions, over-the-counter medications, herbal supplements, and vitamins.
If you are of reproductive potential, you have risk for fetal harm. Use effective contraception during treatment and at least one week after the last dose. Do not breastfeed while on treatment. This medication may impair your fertility.
Review the drug’s adverse reactions and parameters of when to call and report any symptoms.
Special Population Considerations
No clinically significant differences in patients aged 65 or older compared to younger patients were noted in the drug’s trials. The drug was not tested on individuals with severe renal or hepatic impairment. Before initiating treatment with patients with impaired renal or hepatic function, consider the risks and benefits.
Because of a risk for fetal harm, belumosudil requires safe handling during administration and disposal.
Kadmon ASSIST is available Monday–Friday from 8 am–8 pm EST. Visit their website or call 844-KADMON1 (523-6661).