Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data

• In patients treated with deferiprone, ANC levels below 0.2×109/L conferred the highest risk of serious infections.

• An ANC of less than 0.2×109/L may be a clinically relevant threshold to define agranulocytosis with a high risk of infection.

Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug-induced neutropenia (IDIN) that may put them at risk of infection. The purpose of this analysis was to examine the rates of severe IDIN and risk of serious infections at different ANC levels in patients treated with deferiprone. Events of severe IDIN (ANC <0.5×109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by 3 discrete ANC levels: Group 1, 0.2-0.5×109/L; Group 2, 0.1-0.199×109/L; Group 3, <0.1×109/L. In clinical trials, 22 events of severe IDIN were observed (Group 1, n=9; Group 2, n=3; Group 3, n=10); total deferiprone exposure was 1990.26 patient-years; and rates of severe IDIN per 100 patient-years were 0.45 in Group 1, 0.15 in Group 2, and 0.50 in Group 3. All serious infections were in Group 3 (3/10, 30.0%). In the postmarketing setting, 176 events of severe IDIN were reported (Group 1, n=65; Group 2, n=20; Group 3, n=91); total deferiprone exposure was 111,570.24 patient-years; and rates of severe IDIN per 100 patient-years were 0.06 in Group 1, 0.02 in Group 2, and 0.08 in Group 3. Rates of serious infection were 7.7% (n=5/65) in Group 1, 10% (n=2/20) in Group 2, and 13.2% (n=12/91) in Group 3. Our findings suggest that in patients receiving deferiprone, ANC below 0.2×109/L carries a high risk of serious infections, consistent with the recent neutropenia guidelines that agranulocytosis with ANC <0.2×109/L is associated with a high risk of serious infections.