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

Sherif M. Badawy; Jan Palmblad; Fernando Tricta; Noemi Toiber Temin; Caroline Fradette; Leo Lin; Anna Rozova; Sujit Sheth

doi:10.1182/bloodadvances.2023012316

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

Sherif M. Badawy, Jan Palmblad, Fernando Tricta, Noemi Toiber Temin, Caroline Fradette, Leo Lin, Anna Rozova, Sujit Sheth^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug–induced neutropenia (IDIN) that may increase risk of infection. This analysis examined the rates of severe IDIN and risk of serious infections at different absolute neutrophil count (ANC) levels during deferiprone treatment. Events of severe IDIN (ANC <0.5 × 10⁹/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by discrete ANC levels: group 1, 0.2 × 10⁹/L to 0.5 × 10⁹/L; group 2, 0.1 × 10⁹/L to 0.199 × 10⁹/L; group 3, <0.1 × 10⁹/L. In clinical trials, 22 events of severe IDIN occurred (group 1, n = 9; group 2, n = 3; group 3, n = 10), 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 (1990.26 patient-years deferiprone exposure). 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) 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 (111 570.24 patient-years deferiprone exposure). Rates of serious infection were 7.7% (5/65) in group 1; 10% (2/20) in group 2; and 13.2% (12/91) in group 3. Our findings suggest a high risk of serious infections with ANC <0.2 × 10⁹/L during deferiprone treatment, a level consistent with the recent neutropenia guidelines.

Original language	English (US)
Pages (from-to)	5641-5649
Number of pages	9
Journal	Blood Advances
Volume	8
Issue number	21
DOIs	https://doi.org/10.1182/bloodadvances.2023012316
State	Published - Nov 12 2024

Funding

The authors thank all the patients, their families, and the investigators involved in the deferiprone clinical-development program. Medical writing support was provided by Sangeeta Chakraborty and Michael Dyle, contracted by Oxford PharmaGenesis Inc, with funding from Chiesi USA, Inc. The study was sponsored by Chiesi Global Rare Diseases (formerly ApoPharma Inc).

ASJC Scopus subject areas

Hematology

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10.1182/bloodadvances.2023012316

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

abstract = "Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug–induced neutropenia (IDIN) that may increase risk of infection. This analysis examined the rates of severe IDIN and risk of serious infections at different absolute neutrophil count (ANC) levels during deferiprone treatment. Events of severe IDIN (ANC <0.5 × 109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by discrete ANC levels: group 1, 0.2 × 109/L to 0.5 × 109/L; group 2, 0.1 × 109/L to 0.199 × 109/L; group 3, <0.1 × 109/L. In clinical trials, 22 events of severe IDIN occurred (group 1, n = 9; group 2, n = 3; group 3, n = 10), 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 (1990.26 patient-years deferiprone exposure). 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) 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 (111 570.24 patient-years deferiprone exposure). Rates of serious infection were 7.7% (5/65) in group 1; 10% (2/20) in group 2; and 13.2% (12/91) in group 3. Our findings suggest a high risk of serious infections with ANC <0.2 × 109/L during deferiprone treatment, a level consistent with the recent neutropenia guidelines.",

author = "Badawy, {Sherif M.} and Jan Palmblad and Fernando Tricta and Temin, {Noemi Toiber} and Caroline Fradette and Leo Lin and Anna Rozova and Sujit Sheth",

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AU - Badawy, Sherif M.

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AU - Temin, Noemi Toiber

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AU - Lin, Leo

AU - Rozova, Anna

AU - Sheth, Sujit

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AB - Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug–induced neutropenia (IDIN) that may increase risk of infection. This analysis examined the rates of severe IDIN and risk of serious infections at different absolute neutrophil count (ANC) levels during deferiprone treatment. Events of severe IDIN (ANC <0.5 × 109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by discrete ANC levels: group 1, 0.2 × 109/L to 0.5 × 109/L; group 2, 0.1 × 109/L to 0.199 × 109/L; group 3, <0.1 × 109/L. In clinical trials, 22 events of severe IDIN occurred (group 1, n = 9; group 2, n = 3; group 3, n = 10), 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 (1990.26 patient-years deferiprone exposure). 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) 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 (111 570.24 patient-years deferiprone exposure). Rates of serious infection were 7.7% (5/65) in group 1; 10% (2/20) in group 2; and 13.2% (12/91) in group 3. Our findings suggest a high risk of serious infections with ANC <0.2 × 109/L during deferiprone treatment, a level consistent with the recent neutropenia guidelines.

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

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