Ruxolitinib treatment for patients with steroid-refractory GvHD following hematopoietic stem cell transplantation

The management of patients with corticosteroid-refractory (SR) graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) remains a clinical challenge, and significantly contributes to the rate of non-relapse mortality (NRM).¹ Ruxolitinib is an oral, Janus-associated kinase 1 and 2 inhibitor (JAK1, JAK2), which has been shown to be effective in treating SR GvHD.² However, only limited data exists regarding complications of ruxolitinib use.

Dr. Sameem Abedin, from the Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, US, and colleagues, published results from a single-centre, retrospective analysis examining outcomes and infection related events for patients (n = 43) with SR GvHD treated with ruxolitinib.³

Patients and methods

• For patients with acute SR GvHD (n = 19), ruxolitinib (5 mg, oral, twice daily) was given for three days, with dose modifications allowed after this time up to 10 mg
• Patients with chronic SR GvHD (n = 24), received ruxolitinib at a dose of 10 mg twice daily

Key findings

Efficacy

• Median follow-up from initiation of ruxolitinib therapy: 163 days (range, 12–658)
• Median time to initiation of ruxolitinib post-HSCT: 93 days (range, 24–265)
• Median time to initiation of ruxolitinib following onset of acute SR GvHD: 21 days (range, 3–162)
• At day 28 following start of ruxolitinib therapy, 84% of patients with acute SR GvHD achieved either a complete response (CR) or partial response (PR)
• Best overall response rate in patients with acute SR GvHD: 89% (17/19)
  • Responses include 12 CR and 5 PR
• Median duration of therapy for patients with acute SR GvHD: 90 days (range, 11–630)
• Estimated 6-month failure-free survival rate for patients with acute SR GvHD: 58% (95% CI, 39–85)
• Response to ruxolitinib therapy in patients with chronic SR GvHD: 83% (20/24)
  • Responses include 3 CR and 17 patients with improvement in one organ system
• Median duration of therapy for patients with chronic SR GvHD: 166 days (range, 60–932)
• Estimated 6-month failure-free survival rate for patients with chronic SR GvHD: 88% (95% CI, 75–100)

Safety

• The rate of cytopenia was higher amongst patients with acute SR GvHD compared to chronic SR GvHD: 36% vs 17%
• For the total patient population, infections during ruxolitinib therapy were seen in 42% (18/43) of patients
• Median time to infection following start of ruxolitinib therapy: 34 days (range, 9–197)
• Incidence rate of infections for patients treated with ruxolitinib: 0.41 infections/100 days
  • In patients with acute SR GvHD, rate of infection: 1.1 infections/100 days
  • In patients with chronic SR GvHD rate of infection: 0.15 infections/100 days
• Patients with acute SR GvHD developing ≥ 1 infection post ruxolitinib initiation: 68% (13/19)
• Patients with chronic SR GvHD who experienced infection: 21% (5/24)

In conclusion, the results from this study support the role of ruxolitinib in the management of patients with SR GvHD, meanwhile demonstrating the importance for infection monitoring. Moreover, the study authors concluded that ongoing data collection is required for patients receiving treatment with ruxolitinib, with careful consideration regarding antibacterial prophylaxis and viral reactivation.