Abstract 3541

Background

One of the concerns of potential adverse reactions of thrombopoietin receptor (MPL) agonists (romiplostim and eltrombopag) is development of myeloid malignancies. Progression from myelodysplastic syndrome to acute myelogenous leukemia (AML) has been reported in romiplostim. However, development of AML in immune thrombocytopenia (ITP) patients has not been reported. The objective of this study is to clarify whether the concern of AML in MPL agonists in patients with ITP is worth further investigation.

Method

We performed a disproportionality analysis on patients with ITP registered in an adverse event database, AERS between 2002 and 2011. We compared characteristics between AML case and others.

Results

Total of 4,821 subjects were identified as ITP and 62 AML cases among them in the AERS. The proportion of AML reporting in romiplostim and eltrombopag were 1.73% (95%CI; 1.30–2.26%) and 1.35% (0.62–2.54%), respectively. It should be noted that all AML was reported with one or more MPL agonist(s). Other factors associated with AML were male gender (OR 2.01; 95%CI 1.03–3.91) and age between 60 and 69 (OR 2.22; 95%CI 1.16–4.24).

Conclusion

We reported possible association between AML and MPL agonist use in ITP subjects. Due to limitations of spontaneous reporting, further studies are warranted to determine whether the detected signal is real risk or not. Prescribing physicians should not alter their prescribing behaviors based on only this preliminary analysis.

Table.

Logistic Regression Model for AML*

VariableCoefficient betaStandard ErrorWald kai squareAdjusted Odds Ratio
[95% Confidence Interval]
(Intercept) −7.46 0.89  – – P-value 
Romiplostim 1.31 0.57 2.29 3.70 [1.18–11.63] 0.022 
Eltrombopag 0.65 0.54 1.21 1.92 [0.65–5.70] 0.228 
Male 0.70 0.33 2.10 2.01 [1.03–3.91] 0.036 
Reporting in 2010–11 1.03 0.61 1.68 2.80 [0.82–9.56] 0.093 
Report from USA 0.78 0.61 1.28 2.18 [0.64–7.41] 0.202 
Age 60–69 0.80 0.32 2.45 2.22 [1.16–4.24] 0.014 
VariableCoefficient betaStandard ErrorWald kai squareAdjusted Odds Ratio
[95% Confidence Interval]
(Intercept) −7.46 0.89  – – P-value 
Romiplostim 1.31 0.57 2.29 3.70 [1.18–11.63] 0.022 
Eltrombopag 0.65 0.54 1.21 1.92 [0.65–5.70] 0.228 
Male 0.70 0.33 2.10 2.01 [1.03–3.91] 0.036 
Reporting in 2010–11 1.03 0.61 1.68 2.80 [0.82–9.56] 0.093 
Report from USA 0.78 0.61 1.28 2.18 [0.64–7.41] 0.202 
Age 60–69 0.80 0.32 2.45 2.22 [1.16–4.24] 0.014 
*

Record with missig data in gender, age or reporting country are removed from the modeling resulting in 2,779 degree of freedom.

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Disclosures:

Tojo:Novartis Pharma K.K.: Research Funding; Bristol-Myers Squibb Company: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Dainippon Sumitomo Pharma Co., Ltd.: Research Funding; Celgene K.K.: Consultancy. Yasuo:sanofi-aventis K.K.: Employment.

Topics:
leukemia, myelocytic, acute, thrombocytopenia due to immune destruction, thrombopoietin receptor agonists, inosine triphosphate, purpura, thrombocytopenic, idiopathic, agonists, romiplostim, eltrombopag, adverse effects, adverse event

Author notes

*

Asterisk with author names denotes non-ASH members.

This icon denotes a clinically relevant abstract

© 2012 by The American Society of Hematology
2012
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