Clinical Outcomes of Ruxolitinib in the Salvage Treatment of Chronic Graft-Versus-Host Disease

Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for malignant and non-malignant hematological diseases. Chronic Graft-versus-Host Disease (cGVHD) is a major contributor to late morbidity and mortality, significantly affects patients' quality of life.The first-line systemic therapy is corticosteroid,but 40%-60% patients need second-line or additional treatments. Available second-line therapies such as cyclosporine, mycophenolate mofetil, methotrexate, tacrolimus and sirolimus are less than ideal.

Ruxolitinib is is an orally selective JAK1 and JAK2 inhibitor that has been approved by the FDA for the treatment of myelofibrosis. Prospective phase II and III trials using Ruxolitinib have demonstrated that it's effective and safe in the treatment of cGVHD. In this report, we share the clinical outcomes of using Ruxolitinib as salvage treatment of cGVHD.

Methods

This is a retrospective study of 39 patients with cGVHD who received Ruxolitinib as salvage treatment after failure of first-line or second-line therapies given at least one week.All patients were informed of the off-label use of Ruxolitinib and provided informed consent. Patients were treated with Ruxolitinib orally as an add-on immunosuppressive therapy(5mg twice daily if body weight ≥ 25kg and 2.5mg twice daily if body weight <25kg).If their cGVHD improved,2.5 mg was reduced weekly until withdrawal.Patients were monitored weekly for blood test and cytomegalovirus (CMV) DNA.

Results

Among the 39 patients,19 were male (48.7%) and 20 were female(51.3%). According to the 2015 NIH cGVHD diagnosis and staging criteria, 10 patients had mild,14 patients had moderate and 15 patients had severe cGVHD.The median time of cGVHD was 112 days (range 38-2000 days),the median time of Ruxolitinib taken was 56 (7-154) days,the median follow-up time was 221 (33-312) days,and the median time of Ruxolitinib taking effect was 14 (7-28) days.All patients tolerated Ruxolitinib well.According to the 2015 NIH cGVHD therapeutic response criteria,the overall response rate was 84.6%, including complete remission (CR) in 24 (59% )and partial response (PR) in 10 (25.6%). However,four patients (10.3%) had no response (NR) and two patients (5.1%) had disease progression. The organ responses (CR+PR) were as follows: skin 19/21 (90.5%),gastrointestinal tract 5/6 (83.3%),liver 5/6 (83.3%),lung 8/11(72.7%),hematologic 1/1(100%),mouth 3/5(60%),eyes 4/8 (50%),genitourinary tract 0/2 (0%),and musculoskeletal 0/1(0%).Among the adverse effects,eight cases (20.5%) had CMV reactivation and was controlled with antiviral therapy,ten cases (25.6%)had cytopenia, six cases (15.4%)had cGVHD relapse after Ruxolitinib was discontinued,two cases (5.1%) developed relapse of primary disease, and three cases (8%) died of pulmonary infection.

Conclusions

Low-dose of Ruxolitinib was effective to refractory cGVHD with good drug tolerance and controllable adverse effects. Ruxolitinib is expected to be a first- or second-line treatment for cGVHD but requires a randomized controlled trial.