Preemptive Administration of Ruxolitinib Rapidly Ameliorate Gvhd after Allo-Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study

Objective:

Clinical benefit with ruxolitinib as a salvage therapeutic agent in steroid-refractory acute graft-versus-host disease (aGVHD) has been reported. The purpose of this study is to explore the efficacy and safety profile of preemptive administration of ruxolitinib for patients with GVHD after hematopoietic stem cell transplantation (HSCT), and to determine the optimal timing of start of ruxolitinib treatment.

Methods:

We conducted a single-center retrospective study to analyze the overall response rate at day 28 and the amelioration of GVHD after preemptive treatment of ruxolitinib in patients with GVHD post-HSCT. A total of 35 patients (26 males/ 9 females) with GVHD (30 aGVHD/ 5 cGVHD) treated at Fujian Medical University Union Hospital (Fuzhou, China) from July 2016 to April 2019 were enrolled. All patients received conditioning regimens including ATG, cyclosporine A, methylprednisolone, methotrexate mycophenolate mofetil w/o basiliximab for prevention of GVHD. Ruxolitinib was administered orally at 10 mg twice daily for patients ≥ 40 kg or 5 mg twice daily if <40 kg. The patients were divided into 3 groups according to the starting time of GVHD treatment with the preemptive ruxolitinib: shorter than 3 days (≤3 day,13, 37.1%), between days 3-7 (3-7 days,10, 28.6%) and more than 7 days(>7 days,12, 34.3%). Treatment responses of ruxolitinib and the safety are compared among groups.

Results:

These three groups were well matched demographically. There were no significant differences in conditioning regimens, donor types, CD34+ cells infusion, GVHD prophylaxis regimens and primary treatment among 3 groups. The median time to response of ≤3 days group, 3-7 days group and >7 days group was 20.5 (6-43) , 19.5 (2-107) and 20.5 (9-60) days, respectively. The ≤3 d group showed a best overall response rate (ORR) and complete remission rate (CRR) at day 28 after treatment than 3-7 d group and >7 d group (ORR: 92.3% vs 90.0% vs 83.3%, P=0.361; CRR: 46.2% vs 40.0% vs 25.0%, P=0.512 ). The cumulative complete remission rates among 3 groups were 58.5% (≤3 d group), 86.7% (3-7 d group) and 25% (>7 d group), respectively (P=0.096). The severity of GVHD were significantly ameliorated at day 28 in ≤3 d group than the other 2 groups ( 92.3% vs 70.0% vs 50.0%, P=0.064), and moreover, the clinical GVHD scores dropped significantly in ≤3 d group than >7 d group (-1.54 grade vs -0.75 grade, P=0.041) at day 28 after treatment. Incidence and severity of adverse reactions did not differ significantly between groups (P>0.05).

Conclusion:

When preemptive administration ruxolitinib is initiated rapidly, remarkable efficacy on amelioration of GVHD can be achieved without significant adverse effects. Larger randomized trials are needed to confirm efficacy.