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Pharmacovigilance Study of Pancytopenia in Patients Receiving PARP Inhibitors


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In a study reported in a research letter in JAMA Oncology, Morice et al found that pancytopenia was associated with use of poly (ADP-ribose) polymerase (PARP) inhibitors for cancer treatment, according to drug adverse event reports in the World Health Organization global pharmacovigilance database VigiBase.

Study Details

The study involved data on individual drug adverse events reported in VigiBase from the first report of a PARP inhibitor–related adverse event in 2009 through March 2021. PARP inhibitors included in the analysis were olaparib, rucaparib, niraparib, talazoparib, and veliparib. Overall, 23,305 adverse events associated with the five PARP inhibitors and 20,269,537 adverse events associated with any drugs were reported during this period. Risk of pancytopenia was expressed as reporting odds ratio, representing observed and expected drug-adverse events associations using the full VigiBase database as the comparator.

Key Findings

Pancytopenia was significantly associated with the PARP inhibitor drug class, with 201 reports of pancytopenia in the database (reporting odds ratio [ROR] = 5.5, 95% confidence interval [CI] = 4.6–6.7). Among the 201 reports, 194 (97%) were for serious pancytopenia.

To our knowledge, this work is the first to highlight a substantial association between PARP inhibitor class and an increased risk of reported pancytopenia. Our results indicate that half of the patients in this study with available data had an early onset of pancytopenia within the first 2 months after the initiation of PARP inhibitor treatment for cancer, suggesting the need for enhanced blood surveillance.
— Morice et al

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The association of pancytopenia was significant for each PARP inhibitor included in the analysis, with reporting odds ratios of 17.4 (95% CI = 8.9–34.0) for talazoparib, 6.8 (95% CI = 5.3–8.9) for niraparib, 5.3 (95% CI = 3.7–7.6) for olaparib, 8.2 (95% CI = 2.5–27.1) for veliparib, and 2.2 (95% CI = 1.2–4.0) for rucaparib.

Among 48 patients with available data, median time to onset of pancytopenia from start of PARP inhibitor exposure was 1.6 months (interquartile range [IQR] = 0.7–11.0 months, range = 0.2–29.9 months).

Among 20 patients with available data, median duration of pancytopenia was 1.5 months (IQR = 0.9–3.1 months, range = 0.4–9.0 months)

Among 157 patients with known treatment management, 72% discontinued treatment, 17% were given a dose reduction, and dosing was unchanged in 11%.

Among 146 patients with adverse events co-reported with pancytopenia, 18 (12%) reported myelodysplastic syndrome or acute myeloid leukemia.  

Among 117 patients with known outcome, 59% had recovered or were recovering, 26% had not recovered, and 15% had died.

The investigators stated, “To our knowledge, this work is the first to highlight a substantial association between PARP inhibitor class and an increased risk of reported pancytopenia. Our results indicate that half of the patients in this study with available data had an early onset of pancytopenia within the first 2 months after the initiation of PARP inhibitor treatment for cancer, suggesting the need for enhanced blood surveillance.”

Joachim Alexandre, MD, PhD, of the Department of Pharmacology, Caen University Hospital, Normandie University, Caen, France, is the corresponding author for the JAMA Oncology article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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