CHRONOS: Real-world outcomes with third-line therapy in steroid- and ruxolitinib-refractory GI-aGvHD

Results from CHRONOS, a multicenter, international, non-interventional, retrospective cohort study evaluating real-world outcomes with third-line systemic therapy in adults with steroid- and ruxolitinib-refractory acute graft-versus-host disease (aGvHD) with gastrointestinal (GI) involvement (GI-aGvHD; N = 59), were published in Bone Marrow Transplantation by Clausen et al. The primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around Day 28; secondary endpoints included duration of response (DoR), real-world progression-free survival (rwPFS), and overall survival (OS).

Key data: Patients received various therapies in the third-line setting, the most common being extracorporeal photopheresis (ECP; 29%), etanercept (24%), and vedolizumab (17%). The Day 28 all-organ ORR was 36% (95% confidence interval [CI], 24–49), and the GI-ORR was 37% (95% CI, 25–51); 29% and 52% of responders lost response within 30 and 90 days, respectively. By Day 56, all-organ ORR was 20% (95% CI, 11–33) and GI-ORR was 22% (95% CI, 12–35). Median rwPFS and OS were both 86 days (95% CI, 54–128); median OS was 186 days in Day 28 responders vs 45 days in non-responders. Grade ≥2 infectious events occurred in 51% of patients within 3 months, while Grade 3–4 thrombocytopenia and neutropenia in the same period occurred in 64% and 32%, respectively.

Key learning: Third-line therapy demonstrated limited effectiveness in patients with steroid- and ruxolitinib-refractory GI-aGvHD, underscoring the need for novel therapeutic approaches in this high-risk population.