Clinical outcomes of third-line therapy for aGvHD with gastrointestinal involvement after steroids and ruxolitinib failure.

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24-49%), GI-ORR was 37% (95% CI: 25-51%); 29% (95% CI: 11-49%) of responders lost response within 30 days, and 52% (95% CI: 29-72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54-128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3-4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.