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

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.

Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis.

BACKGROUND: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 10(9)/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real-life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis. PROCEDURE: This non-interventional surveillance program assessed the monitoring of deferiprone therapy in clinical practice. A total of 294 patients with transfusion-dependent anemias received deferiprone, as monotherapy or with another chelator, for up to 1 year. The participating physicians were not given any instructions about treatment and monitoring beyond being referred to the information in the package insert. RESULTS: ANC monitoring was conducted at an average interval of 5 ± 4 weeks, and deferiprone was not always interrupted upon detection of neutropenia. One patient (0.3%) experienced agranulocytosis, and nine others (3%) experienced a total of 11 episodes of neutropenia. All neutropenia episodes resolved; median time to resolution was similar whether or not treatment was interrupted; and no case of neutropenia progressed to agranulocytosis. CONCLUSIONS: These data indicate that less frequent ANC monitoring and continuation of deferiprone therapy during neutropenia are not associated with prolonged neutropenia or with progression to agranulocytosis.