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M.D. Cappellini et al.
two achieved a mean hemoglobin increase of ≥1 g/dL sus- tained for ≥12 weeks.
levels were lower than pretransfusion levels. The remain- ing three (19%) patients (2 receiving 0.75 mg/kg sotater- cept, 1 receiving 0.3 mg/kg sotatercept) experienced an increase in transfusion frequency, requiring between 0.7- 1.0 additional transfusions per 24 weeks, representing an increase of 6.7-17.2% from baseline. Based on the observed responses, the active starting dose of sotatercept in patients with TDT was ≥0.5 mg/kg.
Bilirubin
For NTDT patients, indirect bilirubin and total bilirubin decreased by 5-25% for patients receiving 0.3, 0.75, and 1.0 mg/kg (Online Supplementary Figure S2A). Among TDT patients with available bilirubin data at baseline, indirect bilirubin and total bilirubin increased by between 15% and 80% during treatment versus baseline at all dose levels (Online Supplementary Figure S2B). However, the changes were not statistically significant, and there was wide vari- ability in the level of change.
B
Transfusion-dependent b-thalassemia patients
Of 16 patients with TDT treated with sotatercept, ten
(63%) achieved a transfusion burden reduction of ≥20% sustained for ≥24 weeks; seven patients (44%) achieved a reduction of ≥33%, and two patients (13%), a reduction of ≥50% (Figure 3). Five of the ten patients achieved transfu- sion burden reduction while maintaining stable or improved hemoglobin levels at 12 weeks. The mean change in hemoglobin level from baseline to the end of treatment was 0.7 g/dL in all patients with TDT. Nine patients (56%) achieved a reduction in transfusion fre- quency over 24 weeks, receiving fewer transfusions per 24 weeks during treatment, while maintaining stable or improved hemoglobin levels versus pretransfusion levels. Four patients (25%) also achieved a reduction in transfu- sion frequency over 24 weeks; however, their hemoglobin
A
Figure 1. Response to sotatercept treatment in patients with non-transfusion-dependent β-thalassemia. (A) Percentage of sotatercept-treated non-transfusion- dependent b-thalassemia patients achieving mean hemoglobin level increases from baseline of ≥1.0 g/dL and ≥1.5 g/dL sustained for ≥12 weeks by assigned dose group. (B) Average maximum increase in hemoglobin levels within 12 weeks versus baseline levels in responders versus non-responders by dose group. Responders were those patients achieving a ≥1.0 g/dL increase in hemoglobin levels sustained for ≥12 weeks. Error bars show the standard deviation of the mean. Hb: hemo- globin.
Figure 2. Mean change in hemoglo- bin levels from baseline up to day 400 in patients with non-transfu- sion-dependent b-thalassemia treated with different doses of sotatercept. Data are presented by assigned dose level, prior to intrap- atient dose escalation. Hb: hemo- globin.
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haematologica | 2019; 104(3)