Hematological toxicity of parp inhibitors in solid tumors: a systematic review and safety meta-analysis

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) are effective agents in different tumor types. A typical class of adverse events (AEs) associated with these agents, often leading to treatment modifications and discontinuations of treatment, is hematological toxicity. In our systematic review and safety meta-analysis, we investigated the incidence and risk of all grades and ≥ grade (G) 3 hematological AEs, including anemia, neutropenia, thrombocytopenia, and acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) due to PARPis, used alone or in combination, in patients diagnosed with solid tumors. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology, and the European Society of Medical Oncology meeting abstracts for randomized clinical trials (RCTs) concerning the use of PARPis in patients with solid tumors. The search deadline was April 30, 2024. We calculated risk ratios (RRs) for all-grade and ≥ G3 AEs of PARPis versus non-PARPis. 31 phase II/III RCTs were included. Anemia was the most common all-grade (49.2%) and ≥ G3 AE (25.0%). The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.15, p < 0.00001), neutropenia (RR = 1.50, p = 0.0002), and thrombocytopenia (RR = 2.59, p < 0.00001) compared to non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.43, p < 0.00001), neutropenia (RR = 1.70, p = 0.002), and thrombocytopenia (RR = 5.42, p < 0.00001) was detected. PARPis did not increase the risk of AML/MDS (p = 0.86). PARPis increase the risk of hematologic toxicity compared to other treatments in solid tumors. Clinicians should be aware of this risk, especially given the expected increase in PARPis use in the next year in different tumor types.