MDS, AML a Risk With PARP Inhibitors in BRCA Mutation Carriers

What is the concern behind PARP inhibitors and leukemia? — Name withheld on request

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been reported in patients receiving poly(ADP-ribose) polymerase (PARP) inhibitors such as olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula). Warnings about MDS or AML are listed in the prescribing information for the above the PARP inhibitors currently used in the United States.

MDS or AML has been reported in 0.5% to 2% of patients taking the various approved PARP inhibitors. Reports indicate that the patients had received prior treatment with platinum-based chemotherapy or other DNA-damaging agents, and most of the cases of MDS and AML were reported in patients with BRCA mutations.

BRCA gene is involved with repair of DNA damage, and defects in DNA repair may increase the risk of developing MDS or AML. Because of this, MDS or AML are more of a concern in patients with BRCA mutations.

Regular monthly monitoring of complete blood counts (CBC) are recommended for patients taking PARP inhibitors. Patients with prolonged hematologic abnormalities should undergo further evaluation. If the patient develops MDS or AML, the PARP inhibitor should be discontinued.