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PARP Inhibitors Increase Risk for MDS, AML

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Treatment with poly-ADP ribose polymerase (PARP) inhibitors comes with an elevated real-world risk of myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML), according to research published in Frontiers in Pharmacology.

Researchers led by Quanfeng Zhao of Army Medical University in Chongqing, China, reviewed the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the EudraVigilance (EV) database for adverse event reports related to four PARP inhibitors. Over the seven-year period assessed by the study, the PARP inhibitors had a significant and disproportionate association as a drug class with MDS or AML.

The researchers determined that MDS and AML usually emerged after long-term treatment and had high mortality rates.

“Our findings provide objective evidence for the postmarketing safety of PARP inhibitors,” the authors wrote.

PARP inhibitors have produced significant clinical benefits for treating a variety of cancers, but these drugs have also been associated with rare serious adverse events and have an FDA warning on their labels.

To understand the toxicity profiles of PARP inhibitors, researchers used three different data mining algorithms to analyze adverse event reports for four different PARP inhibitors: olaparib, niraparib, rucaparib, and talazoparib.

Reports were gathered from the FAERS and EV databases between October 1, 2014, and September 30, 2021. Of the 16,710 adverse event reports for PARP inhibitors in the FAERS databases, 332 were associated with MDS or AML. Additionally, 349 of the 11,937 adverse event reports for PARP inhibitors in the EV database were associated with MDS and AML.

“Based on the criteria used for the three algorithms, a significant disproportionate association was found between PARP inhibitors as a drug class and MDS/AML,” the authors wrote.

The median latency of MDS associated with PARP inhibitors was 211 days, while AML had a median latency of 355 days. MDS associated with PARP inhibitors had a mean mortality rate of 37.96% in the FAERS database and 5.8% in the FAERS database.

AML caused by PARP inhibitors had an average fatality rate of 60.4% in the FAERS database and 12.2% in the EV database.

Researchers also found that the PARP inhibitors had a much higher risk for MDS than for AML. As for the individual PARP inhibitors, the authors found that olaparib had a stronger association with MDS and AML than the other inhibitors.

“In the real world, PARP inhibitors increase the risk of MDS and AML, which can result in high mortality and tend to occur during long-term use,” the authors concluded.

Zhao Q, Ma P, Fu P, et al. Myelodysplastic syndrome/acute myeloid leukemia following the use of poly-adp ribose polymerase (parp) inhibitors: a real-world analysis of postmarketing surveillance data. Front Pharmacol. 2022. doi:10.3389/fphar.2022.912256

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