PARP inhibitors were found to increase the risk of developing secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), according to the results of a systematic review and safety meta-analysis reported in The Lancet Haematology.

The evaluation included 28 randomized controlled trials (RCTs) involving PARP inhibitors in various disease settings. Most of the RCTs tested PARP inhibitors in ovarian cancer (12 trials), followed by breast cancer (5 trials). PARP inhibition was also evaluated in lung, gastric, pancreatic, colorectal, and prostate cancer, as well as melanoma. The most commonly studied PARP inhibitors were olaparib (13 trials) and veliparib (11 trials).

Among 18 placebo-controlled trials encompassing 7307 patients,

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PARP inhibitors “significantly increased the risk of myelodysplastic syndrome and acute myeloid leukemia” vs placebo treatment (odds ratio [OR], 2.63; 95% CI, 1.13–6.14; P=0.026). Cases of secondary MDS and AML were seen only in ovarian cancer trials.

Overall, 21 cases of MDS and AML were seen among patients who received PARP inhibitors, translating to a total incidence rate of 0.73% (21 events of 4533 patients; 95% CI, 0.50-1.07; P =.87). Across placebo groups, the incidence of MDS and AML was 0.47% (3 events of 4533 patients; 95% CI, 0.26-0.85; P =1.00).

A search of VigiBase, the World Health Organization’s pharmacovigilance database, identified 178 cases of MDS and AML associated with PARP inhibitor therapy. Retrospective analysis showed that, among cases with available data, the hematologic effects presented within a median of 17.8 months (range, 8.4–29.2 months) of first exposure to PARP inhibition. Nearly half (45%) led to death.

The study authors described MDS and AML cases related to PARP inhibitor therapy as “rare” adverse events associated with a “substantial” proportion of deaths, and encouraged clinicians to remain “vigilant” in evaluating delayed hematologic toxicities in patients receiving PARP inhibitors.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.


Morice P, Leary A, Dolladille C, et al. Myelodysplastic syndrome and acute myeloid leukaemia in patients treated with PARP inhibitors: a safety meta-analysis of randomised controlled trials and a retrospective study of the WHO pharmacovigilance database. Lancet Haematol. Published online December 18, 2020. doi:10.1016/S2352-3026(20)30360-4