What is belumosudil?
Belumosudil is an oral rho-associated, coiled-coil-containing protein kinase (ROCK) inhibitor which primarily inhibits ROCK2, but also ROCK1 to a lesser extent.
How does belumosudil work?
Belumosudil inhibits ROCK2, which downregulates STAT3 phosphorylation, decreases Th17 transcription factors, upregulates STAT5, and shifts Th17/regulatory T-cell balance restoring immune system balance (J Clin Oncol 2021;39(17):1888-1898). This results in downregulation of proinflammatory responses and inhibition of aberrant profibrotic signaling.
What is belumosudil approved for?
Belumosudil is approved for the treatment of patients 12 years and older with chronic graft-versus-host disease (cGVHD) after failing two prior lines of systemic therapy.
What is the basis for this approval?
Belumosudil received approval for treatment of cGVHD based on the Phase II ROCKstar trial (Blood 2021; doi: 10.1182/blood.2021012021). This randomized, open-label, multicenter dose range trial evaluated belumosudil 200 mg daily (n=66) and 200 mg twice daily (n=66) in patients with cGVHD who received 2-5 prior lines of therapy. The median follow up was 14 months. Overall response rates per the 2014 NIH Consensus Criteria were 74 percent (95% CI, 62-84) and 77 percent (95% CI, 65-87) in the 200 mg daily and 200 mg twice daily arms, respectively (Biol Blood Marrow Transplant 2015;21(6):984-999). Median time to response was 5 weeks (range 4-66). Median duration of response was 54 weeks. The 2-year overall survival was 89 percent (95% CI, 82-93).
How do you administer this drug for the treatment of cGVHD?
Belumosudil is administered at a dose of 200 mg by mouth once daily until progression of cGVHD or unacceptable toxicity. Belumosudil should be administered with a meal at the same time each day.
Are there any pre-medications needed?
No antiemetics or other pre-medications are recommended with belumosudil.
What are the common side effects associated with belumosudil (> or =10%)?
The most common adverse events were edema (27%), hypertension (21%), pruritus (11%), skin rash (12%), decreased serum calcium (12%), decreased serum phosphate (28%), increased gamma-glutamyl transferase (21%), abdominal pain (22%), decreased appetite (17%), diarrhea (35%), dysphagia (16%), nausea (42%), decreased hemoglobin (11%), hemorrhage (23%), lymphocytopenia (29%), decreased platelet count (10%), bacterial infections (16%), viral infections (19%), headache (21%), arthralgia (15%), asthenia (46%), muscle spasm (17%), musculoskeletal pain (22%), cough (30%), dyspnea (33%), nasal congestion (12%), and fever (18%).
What are the uncommon side effects associated with belumosudil (<10%)?
Uncommon side effects include increased serum potassium (7%), decreased neutrophils (8%), increased serum alanine aminotransferase (7%), increased serum alkaline phosphatase (9%), and increased serum creatinine (4%).
Are there any important drug interactions I should be aware of?
Belumosudil is a substrate of CYP2C8, CYP2D6, P-glycoprotein/ABCB1, and UGT1A9. Proton pump inhibitors, histamine H2 receptor antagonists, and antacids may decrease the serum concentrations of belumosudil. The dose of belumosudil should be increased to 200 mg by mouth twice daily when co-administered with proton pump inhibitors.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
Mild-to-moderate renal impairment did not have a significant effect on the pharmacokinetics of belumosudil and no dose adjustments are needed. Effects in patients with severe renal impairment, requiring dialysis, or with hepatic impairment are unknown.
Belumosudil should be held in patients who develop with Grade 3 AST or ALT elevation, as well as Grade 2 bilirubin elevation on treatment until liver function resolves to less than or equal to Grade 1. Belumosudil should be permanently discontinued if Grade 4 AST or ALT elevations or Grade 3 or greater bilirubin elevation occurs.
What should my patients know about belumosudil?
* Store at room temperature (68-77[degrees]F) in original container to protect from moisture. Replace cap securely each time after opening. Do not discard desiccant.
* Verify pregnancy status prior to use in patients who may become pregnant. Women who may become pregnant and patients with female partners who may become pregnant should use effective contraception during therapy and for at least 1 week after the last belumosudil dose.
* It is not known if belumosudil is present in breast milk. Breastfeeding is not recommended by the manufacturer during therapy and for at least 1 week after the last belumosudil dose due to the potential for serious adverse reactions.
What useful links are available regarding belumosudil for the treatment of multiple myeloma?
* FDA Approval: https://bit.ly/34alxAH
Any ongoing clinical trials related to belumosudil?
Belumosudil is being studied in patients with moderate-to-severe plaque psoriasis, moderately severe psoriasis vulgaris, and diffuse cutaneous systemic sclerosis.
CHELSEA MINOR, PHARMD, BCPS, BCOP, is Clinical Pharmacist, Hematology and Bone Marrow Transplant at Washington University School of Medicine, St. Louis, Mo. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine, St. Louis, Mo. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.