A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure

Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program

“…The REACH studies also investigated patients with late stage and severe disease (64% stage III–IV aGvHD; 57% had severe cGvHD) [ 14 , 15 ] but the inclusion of pediatric patients (from 2 years old) and the number of patients treated in this CU program, and in other ruxolitinib real-world studies [ 29 – 31 ] have greatly expanded the ruxolitinib-treated population beyond the REACH trial populations ( ≥ 12 years old) [ 14 , 15 ]. Consistent with other CU programs [ 28 – 30 , 32 ] many patients in this study had received multiple lines of therapy and concomitant medications, which highlights the complexity of their disease. Interestingly, ruxolitinib was considered predominantly as a second- or third-line treatment option, which suggests that physicians’ have confidence in the efficacy of ruxolitinib versus investigators’ choice of treatment as demonstrated in patients with steroid-refractory aGvHD and cGvHD in the REACH studies, and its safety in vulnerable patients [ 14 , 15 ].…”

“…However, the tapering off and reductions in corticosteroid doses and usage reported by physicians suggest a steroid-sparing effect with ruxolitinib. Similarly, in other real-world studies with ruxolitinib, corticosteroid dose was reduced in over 60% of adult and pediatric patients with GvHD [ 30 ], whereas at least 75% of patients with cGvHD tapered or discontinued corticosteroids [ 28 , 32 ]; meanwhile, corticosteroid dose was significantly reduced to a tenth of its original dose after 6 months in patients with aGvHD and to nearly a quarter of the original dose after 12 months in patients with cGvHD ( p < 0.001) [ 32 , 35 ]. Collectively, observations from these real-world studies add to the evidence supporting the steroid-sparing effect observed in patients with steroid-refractory/dependent GvHD in REACH2 and REACH3, where patients had consistent reductions in corticosteroid dose over time and more patients discontinued corticosteroids than patients receiving BAT [ 14 , 15 ].…”

“…In addition, a reduced dose of ruxolitinib (5 mg BID) is recommended when patients have severe cytopenia, thrombocytopenia, neutropenia, or elevated total bilirubin, or when administered with strong CYP3A4 inhibitors [ 12 , 13 ]. In other real-world studies of patients with GvHD, a low initial dose of ruxolitinib (5 mg BID) was used in 48–66% of adults in clinical practice, which was subsequently increased to 10 mg BID [ 32 , 35 ]. A dose of 5 mg once daily was used in 18% of patients with aGvHD and 3% of patients with cGvHD in a real-world safety study [ 29 ], whereas tapering of ruxolitinib dose has been reported in 15–38% of patients in other CU studies [ 28 , 30 , 35 ].…”

Updates in chronic graft‐versus‐host disease management

“…22 Finally, a multicenter retrospective study recently evaluates ruxolitinib in a heavily pretreated population (n = 115), since 86% of the patients received ruxolitinib as 4th line or beyond. 23 In this pivotal randomized trial, belumosudil was well tolerated, with no new safety signals. The most common grade 3 or higher AEs were pneumonia (8%), hypertension (6%), and hyperglycemia (5%).…”

“…In addition, in a meta‐analysis that includes 26 studies evaluating ruxolitinib in steroid‐refractory cGvHD, the ORR at any time was 0.78 (95% CI: 0.74–0.81) and the 2‐year OS was 75.3% (95% CI: 68.0%–82.7%) 22 . Finally, a multicenter retrospective study recently evaluates ruxolitinib in a heavily pretreated population ( n = 115), since 86% of the patients received ruxolitinib as 4th line or beyond 23 . With a median follow‐up of 13 months, the ORR was 48.6%, 54.9%, and 48.5% at 3, 6, and 12 months, respectively.…”