Incidence of myelodysplastic syndrome in patients treated with PARP inhibitors: A systematic review.

Abstract

e18583 Background: Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) have revolutionized the treatment landscape for various cancers. However, an increasing body of evidence has highlighted a concerning link between PARPi therapy and the development of myelodysplastic syndrome (MDS). This systematic review aimed to explore the incidence of MDS following PARPi therapy. Methods: A comprehensive literature search was performed on PubMed, Cochrane, EMBASE, Google Scholar, and ClinicalTrials.gov following PRISMA guidelines. After screening 619 articles, twenty-two studies reporting incidences of MDS in adult patients treated with PARPi were included. The inter-study variance was calculated using the DerSimonian-Laird estimator proportions, and a 95% Confidence Interval (CI) was extracted to compute a pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.3.0). Results: A total of 8,153 patients were included for the analysis. The median age was 57 (35-81) years and 99.7% were female. Ovarian cancer was the most common underlying malignancy (81%) followed by breast cancer (19%). BRCA testing data was reported for 5,019 patients and 54% were BRCA1 or BRCA2 positive. Nine studies reported prior chemotherapy, and platinum-based regimens were the most used. Olaparib was the most common used PARPi (47%) followed by Niraparib (15%), Rucaparib (18%), and Veliparib (19%). The median follow-up was 41 (35-81) months and duration of PARPi therapy was ranged from 0.6 to 1.7 years as reported by two of the included studies. In total, 83 out of 8,153 patients (1.01%) were diagnosed with MDS. Niraparib was associated with the highest incidence of MDS (13 patients, 1.5%), followed by Olaparib (30 patients, 1.06%), Rucaparib (5 patients, 0.49%), and Veliparib (2 patients, 0.19%). Conclusions: This systematic review shows that PARPi treatment is associated with an increased incidence of MDS. There is need for continuous monitoring and risk assessment in patients undergoing PARPi therapy to enhance patient safety and improve treatment outcomes.