JAK1/2 Inhibition As a Salvage Therapy for Steroid Refractory Acute and Chronic Graft Versus Host Disease in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients

Introduction: The Jak1/2 inhibitor, ruxolitinib, is effective as a salvage therapy for steroid refractory (SR) graft versus host disease (GVHD) in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. The effectiveness of ruxolitinib for the salvage of SR-GVHD in pediatric HSCT patients has not been studied. Objective: To evaluate ruxolitnib as a salvage therapy for SR- acute GVHD (aGVHD) and chronic GVHD (cGVHD) in pediatric HSCT recipients. Methods: We conducted a retrospective review of pediatric HSCT recipients who received ruxolitinib for treatment of SR-GVHD at our center. SR aGVHD and cGVHD were defined as lack of response to high dose corticosteroids (1-2 mg/kg/day) for 1 and 3 weeks, respectively. Ruxolitnib was administered orally at 5 mg twice daily for patients weighing ≥ 25 kg or 2.5 mg twice daily if Results: Fifteen patients of median age 8.5 years (range 1.6-16.5 years) received ruxolitinib for acute (n=13) and chronic (n=2) GVHD. Transplant characteristics are shown in table 1. aGVHD patients: Grades of aGVHD at time of ruxolitinib administration were grade II (n=2), III (n=9) and IV (n=2). Forty-seven percent (n=6) of patients had acute gastrointestinal (GI) GVHD, 6% (n=1) had acute skin GVHD and the remaining 47% (n=6) had multiple organ involvement. aGVHD was diagnosed at a median of 41 days (20-169 days) and ruxolitinib was started at a median of 147 days (range 55-538 days) after HSCT. Patients received a median of 4 immune suppressive medications (range 1-6) prior to starting ruxolitinib. The median initial dose of ruxolitinib was 5 mg twice daily (range 2.5 mg daily- 5 mg twice daily). Doses were escalated in 11/15 patients, and 9/15 patients reached a maximum dose of 10 mg twice daily. Ruxolitinib was discontinued in 28% (n=3) of patients after 2-9 days and these patients were excluded from response analysis. Patients who received additional immune suppressive agents either 2 weeks prior to starting ruxolitnib (n=2) or after 2 weeks after initiation of ruxolitinib (n=1) were also excluded. Of the 7 evaluable aGVHD patients, 14% (n=1) had CR and 72% (n=5) had PR at a median of 20.5 days from initiation of ruxolitinib. NR was observed in 14 %( n=1) patients. Overall response rate of ruxolitinib was 86%. Durable responses were observed in 43% (n=3) of patients. cGVHD patients: Two patients with severe cGVHD involving skin, eye and GI (n=1), and skin, joints and liver (n=1) received ruxolitinib at 1486 and 2177 days after HSCT, respectively, at a maximum dose of 10 mg twice daily. One patient had PR in 2.5 weeks and one had NR. Adverse effects in all 15 patients included elevated liver enzymes (n=5; 30%), neutropenia (n=8; 53%) and thrombocytopenia (n=4; 26%) leading to discontinuation of ruxolitinib in 10/15 patients. Infectious complications in the 9 patients who were evaluated for responses included EBV viremia (n=2; 22%), adenovirus viremia (n=1; 11%), BK viremia (n=3; 33%), bacterial infections (n=5; 55%) and fungal infections (n=1; 11%). At a median follow up of 341 days (range 260-2331 days) after HSCT 55% (n=5) of patients were alive. Conclusion: Ruxolitinib may have a limited role in the durable salvage of acute and chronic SR-GVHD in pediatric HSCT patients and should be used cautiously in patients with pre-existing liver dysfunction or cytopenia. Future large scale studies may be needed to assess the effectiveness of ruxolitinib in pediatric HSCT patients with SR-GVHD. Disclosures Davies:Novartis: Honoraria.