Long-term follow-up of ruxolitinib pre-approval use in acute and chronic graft-versus-host disease.

Steroid-refractory (SR) acute and chronic graft-versus-host disease (aGVHD/cGVHD) are frequent and serious complications after allogeneic hematopoietic stem cell transplantation. Ruxolitinib (RUX) is approved for the treatment of both conditions. Real world evidence may provide valuable complementary information beyond prospective trials because of significant divergences in study populations, endpoints, treatment strategies, and observation time. We report long-term outcomes of 118 patients with acute (n = 61), classic chronic (n = 43) and overlap chronic GVHD (n = 14) who received RUX within a named-patient-program in the pre-approval era as second-line treatment or beyond. In 22 patients, GVHD occurred after donor lymphocyte infusion (DLI). The cohort included heavily pretreated patients, with 26.2% of aGVHD in 3rd -line or beyond, and 29.8% of cGVHD in 4th -line or beyond. Only 22 patients (18.6%) met all in-/exclusion criteria of the respective pivotal phase III studies. The most frequent incompatibilities were unmet SR criteria, excessive pretreatment, previous DLI, overlap chronic GVHD, and medical/hematological criteria. Overall response rate to RUX was 68.9% in aGVHD, and 66.7% in cGVHD. In all three GVHD types, > 50% of patients were able to discontinue systemic steroids. With a survivors' median follow up of 60.3 months (range, 25.5-99.3) from RUX initiation, 4-year survival probability was 57.4% in aGVHD, 81.1% in classic cGVHD, and 78.6% in overlap cGVHD. Our findings reveal favorable survival probabilities associated with a long-term steroid-sparing/replacing potential of RUX in treatment-refractory aGVHD and cGVHD, including overlap syndrome and DLI-associated GVHD.