What is the treatment for Graft-Versus-Host Disease (GVHD) after treatment with Ibrutinib (ibrutinib)?

From the Guidelines

Ibrutinib at 420 mg daily is a recommended treatment for steroid-refractory chronic Graft-Versus-Host Disease (GVHD), as it has shown efficacy in producing durable responses in patients with multiorgan involvement. The treatment of GVHD after ibrutinib involves a comprehensive approach, considering the patient's history, organ involvement, and response to previous therapies.

Treatment Options

• Corticosteroids, such as prednisone at 1-2 mg/kg/day or methylprednisolone at equivalent doses, are typically used as first-line therapy for GVHD 1.
• For steroid-refractory cases, second-line options include ruxolitinib, tacrolimus, cyclosporine, or extracorporeal photopheresis.
• Given ibrutinib's efficacy in chronic GVHD, as demonstrated in a single-arm multicenter trial with an overall response rate (ORR) of 67% and a sustained response in 71% of responders for at least 20 weeks 1, resuming ibrutinib at 420 mg daily could be considered if not contraindicated.

Considerations

• The choice of therapy depends on GVHD severity, organ involvement, and patient-specific factors, such as history of heart arrhythmias or use of anticoagulation/antiplatelet therapy, which may increase the risk of atrial fibrillation or bleeding with ibrutinib 1.
• Supportive care, including antimicrobial prophylaxis, nutritional support, and symptom management, is essential for patients with GVHD.
• Close monitoring for infections and other complications is necessary, with treatment adjustments based on clinical response, typically evaluated every 1-2 weeks initially.

Adverse Events

• Common adverse events associated with ibrutinib include fatigue, bleeding/bruising, diarrhea, muscle spasms, nausea, thrombocytopenia, and anemia, with grade 3 atrial fibrillation, pneumonia, and diarrhea being notable concerns 1.
• Patients should hold ibrutinib for 3 to 7 days before and after surgical procedures due to the high risk of bleeding 1.

From the FDA Drug Label

1. 4 Chronic Graft versus Host Disease IMBRUVICA is indicated for the treatment of adult and pediatric patients age 1 year and older with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.

The recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2 orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity

The treatment for Graft-Versus-Host Disease (GVHD) after treatment with Ibrutinib (ibrutinib) is Ibrutinib itself, as it is indicated for the treatment of adult and pediatric patients with chronic GVHD after failure of one or more lines of systemic therapy. The recommended dosage is 420 mg orally once daily for patients age 12 years and older, and 240 mg/m2 orally once daily for patients 1 to less than 12 years of age 2.

From the Research

Treatment for Graft-Versus-Host Disease (GVHD) after Ibrutinib

• The treatment for GVHD after ibrutinib involves various approaches, including the use of ibrutinib itself for chronic GVHD 3, 4, 5.
• Ibrutinib has been shown to be effective in treating chronic GVHD, with response rates ranging from 41% to 67% 6, 3.
• The use of ibrutinib in acute GVHD is less established, but a recent case report suggests its potential efficacy in treating severe gastrointestinal acute GVHD 7.
• Other treatment options for GVHD include ruxolitinib, belumosudil, and corticosteroids, which may be used alone or in combination with ibrutinib 5.

Efficacy of Ibrutinib in GVHD

• Ibrutinib has been shown to improve response rates and reduce corticosteroid doses in patients with chronic GVHD 3, 4.
• The median duration of response to ibrutinib in chronic GVHD has been reported to be around 19 months 6.
• Ibrutinib has also been associated with a reduction in plasma levels of soluble factors associated with inflammation, fibrosis, and GVHD 3.

Safety and Toxicity of Ibrutinib in GVHD

• The most common adverse events associated with ibrutinib in GVHD include fatigue, diarrhea, muscle spasms, nausea, and bruising 3, 4.
• Ibrutinib has also been associated with an increased risk of infection, bleeding, and muscle aches 4.
• The safety profile of ibrutinib in GVHD is generally considered acceptable, but close monitoring of patients is recommended to minimize the risk of adverse events 3, 4.