Is There a Place for Anti-Thymocyte Globulin in Steroid-Refractory Acute Graft-Versus-Host Disease??

Acute graft-versus-host disease (aGVHD) remains a fatal complication after allo-HSCT. Acute GVHD resistant to corticosteroids (SR-aGVHD) and ruxolitinib (RUX) negatively affects survival and raises the question of subsequent therapeutic options.

We retrospectively evaluated efficacy and toxicity of rabbit anti-thymocyte globulin (rATG, Thymoglobulin^®, Sanofi) in 16 patients with grade III-IV aGVHD resistant to at least two prior lines of treatment (median 3), including RUX. Patients received rATG at a median total dose of 6 mg/kg (range 3.5-8 mg/kg) for 5 days.

Combined response (CR + PR) was demonstrated in 62.5% of patients (3-CR and 7-PR). Median overall survival (OS) for the whole group was 3.33 months (range 0.96-53.3). rATG-responders showed significantly longer 12-month OS than non-responders (p < 0.05). Most common adverse events during rATG treatment included CMV and BKV reactivations (n = 5; 31.3%), myelosuppression- grade IV thrombocytopenia (n = 9; 56.3%) and grade III-IV granulocytopenia (n = 7; 43.8%). After median follow-up of 3.9 months (range 0.96-53.3), 11 patients died. All non-responders died from aGVHD progression. Among rATG-responders, 3 patients ceased due to infectious complications and 2 because of cerebral hemorrhage.

rATG provides satisfactory response rates in advanced SR-aGVHD failing prior treatments, however non-relapse mortality reduces survival rates among responders.