Do PARPi Increase Blood Cancer Risk in Ovarian Cancer?

TOPLINE:

In a real-world analysis, the relative risk of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) was higher in patients who received chemotherapy plus poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy than in those who received chemotherapy alone for advanced ovarian cancer; however, the absolute risk was low in both treatment groups.

METHODOLOGY:

• This retrospective cohort study analysed data from national cancer registries in England between January 2014 and December 2019 when PARP inhibitors began to be used in clinical practice.
• This study included 11,531 participants with a primary diagnosis of ovarian, fallopian tube, or primary peritoneal cancer and advanced stage III-IV disease who received either chemotherapy plus PARP inhibitor therapy (n = 1529; median age, 63 years) or chemotherapy alone (n = 10,002; median age, 69 years).
• Patients were required to initiate first-line chemotherapy within 90 days of diagnosis, and those receiving PARP inhibitors were required to have a record of two or more cycles of therapy.
• The primary outcome was the secondary diagnosis of MDS or AML within 5 years of completion of first-line chemotherapy, depending on the eligibility period for PARP inhibitor maintenance therapy. The median follow-up duration was 5.87 years.

TAKEAWAY:

• The absolute risk of MDS or AML within 5 years of completion of first-line chemotherapy was 0.33% in patients who received chemotherapy plus PARP inhibitor maintenance therapy and < 0.1% in those who received chemotherapy alone.
• The relative risk of MDS or AML was 2.97 (95% CI, 1.02-8.68; P = .046) in patients who received chemotherapy plus PARP inhibitor maintenance therapy vs chemotherapy alone.
• The median time to diagnosis did not differ significantly between the treatment groups, suggesting that PARP inhibitor therapy was not associated with the faster development of the secondary disease.
• Overall, the incidence of secondary MDS or AML was lower than that reported in previous randomised clinical trials.

IN PRACTICE:

“Relative risk of developing MDS or AML was greater in patients treated with PARPi [PARP inhibitor] maintenance than with chemotherapy alone; however, absolute risk in both groups was low,” the authors wrote. “These findings suggest low incidence of secondary MDS/AML in patients treated with PARPi maintenance therapy; however, clinicians should remain vigilant for patients at high risk of developing these conditions,” they concluded.

SOURCE:

This study was led by Luke Steventon, University College London Hospital NHS Foundation Trust, London, England. It was published online on April 25, 2025, in the European Journal of Cancer.

LIMITATIONS:

The study’s sample size for patients treated with PARP inhibitors was limited, affecting the statistical power needed to compare incidence rates and the time to diagnosis. Additionally, the observational nature of the study may have introduced biases.

DISCLOSURES:

This study did not receive any specific funding. Two authors reported receiving grants and personal fees from various sources. The other authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.