Pre-approval use of ruxolitinib in acute and chronic GvHD: Long-term outcomes from a retrospective study

Results from a single-center, retrospective study evaluating long-term outcomes in patients with treatment-refractory acute graft-versus-host disease (aGvHD; n = 61), classic chronic GvHD (cGvHD; n = 43), or overlap cGvHD (n = 14) who received ruxolitinib were published by Loisl et al. in Annals of Hematology. The cohort was heavily pretreated, with 26.2% of patients with aGvHD and 29.8% of those with cGvHD receiving ruxolitinib in third- or fourth-line therapy or beyond, respectively. Patients received ruxolitinib through a named-patient-program in the pre-approval era between May 2015 and September 2022. The primary endpoint was best overall response rate (ORR) at any time.

Key data: The ORR with ruxolitinib monotherapy was 68.9% in aGvHD, 62.8% in classic cGvHD, and 78.6% in overlap cGvHD. Across all three GvHD types, >50% of patients discontinued systemic steroids. At a median follow-up of 60.3 months from ruxolitinib initiation, 4-year overall survival (OS) was 57.4% in aGvHD, 81.1% in classic cGvHD, and 78.6% in overlap cGvHD. Tolerability of ruxolitinib in the present cohort was comparable to prospective studies, with hematologic toxicities being most frequent, particularly in aGvHD. Any grade infections were common across all groups (77.1% in aGvHD, 76.7% in classic cGvHD, and 71.4% in overlap cGvHD, with Grade 3/4 infections occurring in 49.2%, 30.2%, and 28.6%, respectively.

Key learning: These findings demonstrate favorable long-term outcomes and a potential steroid-sparing effect of ruxolitinib in patients with treatment-refractory aGvHD and cGvHD, including those with overlap syndrome and heavily pretreated GvHD – populations that were excluded from the prospective REACH-2 and REACH-3 trials.