Risk of myelodysplastic syndrome and acute myeloid leukemia related to PARP inhibitor maintenance

Sep 23, 2026

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Objective: estimate the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) attributable to PARP inhibitors (PARPi) based on treatment line in real-world ovarian cancer (OC) patients. Methods: TriNetX platform compared 3402 first-line maintenance PARPi patients with 1653 platinum chemotherapy controls, and 356 PARPi post–platinum-sensitive relapse patients with 1503 controls; cohorts were propensity score matched 1:1 on age, race, bevacizumab, and genetic susceptibility, using hazard ratios for outcomes. Results: first-line showed higher incidence of MDS/AML (1.9% vs 0.1%; HR 2.46; P=.006); no significant differences in the relapse setting and across PARPi types. Conclusions: first-line PARPi maintenance may increase MDS/AML risk.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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Abstract

Objective and Methods

Results and Conclusions

Implications for practice

Introduction

Risk of myelodysplastic syndrome and acute myeloid leukemia related to PARP inhibitor maintenance line in real-world ovarian cancer patients Alberto Farolfi*, 1,, Chiara Casadei1, Nicola Gentili2, SaraTestoni3, Francesca Rusconi4, Emilio Francesco Giunta5, Nicole Brighi5, Giorgia Gurioli6, Daniela Montanari1, Gema Hernandez Ibarburu4, Ugo De Giorgi5 1Medical Oncology, Breast & GYN Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)“Dino Amadori”, Meldola 47014, Italy 2Outcome Research, IRCCS Istituto Romagnolo per lo studio dei Tumori (IRST)“Dino Amadori”, Meldola 47014, Italy 3 Biostatistics and Clinical Trials Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)“Dino Amadori”, Meldola 47014, Italy 4TriNetX, LLC, Cambridge, MA 02140, United States 5Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)“Dino Amadori”, Meldola 47014, Italy 6 Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST)“Dino Amadori”, Meldola 47014, Italy *Corresponding author: Alberto Farolfi, MD, PhD, Medical Oncology, Breast & GYN Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy ([alberto.farolfi@irst.emr.it](alberto.farolfi@irst.emr.it)) . Abstract Objective: To estimate the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) secondary to PARP inhibitors (PARPi), based on the line of treatment, in real-world ovarian cancer (OC) patients. Methods: Using the TriNetX platform, we compared a cohort (experimental A) of 3402 OC patients treated with first-line maintenance PARPi toa control cohort of 1653 OC patients treated with platinum-based chemotherapy without PARPi. Experimental group B included 356 OC patients treated with PARPi after a platinum-sensitive relapse and was compared to a control cohort of 1503 patients who had not received PARPi after 2 lines of platinum-based chemotherapy. The cohorts were propensity score matched (PSM) 1:1 (experimental A vs control 1 and experimental B vs control 2) for age, race, bevacizumab treatment, and genetic susceptibility to neoplasms. A hazard ratio (HR) was used to compare the incidence of MDS and AML between the matched cohorts. Results: In the first-line setting, 2 groups of 1346 matched OC patients (mean age 59.8 ± 10.2 SD) were evaluated. The overall incidence of MDS or AML was 1.9% and 0. 1% in the experimental A and control groups, respectively (HR = 2.46; 95% CI 1.27-4.75, P = .006) . For the platinumsensitive relapse setting, the HR was 1.76 (95% CI 0.42-7.37, P = .432) . No significant differences were observed between the various PARPi used. Conclusions: Our study indicates that PARPi may increase the risk of MDS or AML after first-line maintenance treatment. No significant differences were found across the types of PARPi used. Key words: acute myeloid leukemia; myelodysplastic syndrome; ovarian cancer; PARP inhibitor; real-world evidence. Implications for practice PARP inhibitors (PARPi) have changed the treatment landscape of ovarian cancer; however, major concerns exist about their induced risk to the development of secondary myeloid neoplasms. Furthermore, the duration of their administration varies between the first-line setting, which lasts 2 to 3 years, and the recurrent setting, which lasts until disease progression. Therefore, we evaluated the risk of PARPi-induced secondary myeloid neoplasms in a real-world population, demonstrating a significant increase for first-line treatment, whereas the increase was not statistically significant in the platinum-sensitive relapse setting. No differences were observed across the range of PARPi used. Introduction Poly-ADP-ribose polymerase (PARP) inhibitors, including olaparib, niraparib, rucaparib, and talazoparib, have shown significant clinical benefits in treating various cancers, such as ovarian, breast, pancreatic, and prostate cancers. However, with their increasing a

FAQs

What was the study objective regarding PARP inhibitors and secondary blood cancers?

The study aimed to estimate the risk of MDS and AML associated with PARP inhibitors (PARPi) based on the line of treatment in real-world ovarian cancer patients.

How were the patient groups designed and matched in this research?

Using the TriNetX platform, the study compared PARPi-treated cohorts with control cohorts and applied propensity score matching 1:1 on age, race, bevacizumab use, and genetic susceptibility to neoplasms.

What did the results show for first-line maintenance versus platinum-sensitive relapse settings?

First-line maintenance showed a significant increase in the overall incidence of MDS or AML (1.9% vs 0.1%; HR 2.46; P=.006), while the platinum-sensitive relapse setting did not show a statistically significant difference.

Sep 23, 2026

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