AML and MDS associated with PARP inhibitor treatment of ovarian cancer

I read with interest and concern the publication of O'Malley et al. on exceptional responders in the ARIEL3 study of rucaparib maintenance [ [1] O’Malley D.M. et al. Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma. Gynecol. Oncol. 2022 Oct 20; S0090-8258 (00575–3. (PMID: 36273926)) Google Scholar ]. Of particular note was the information on therapy related myeloid neoplasia (TMN), particularly in light of recent changes in the regulatory landscape for PARP inhibitors in the treatment of ovarian cancer. TMN reporting traditionally includes the hematologic malignancies myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clonal hematopoiesis (CH), the accumulation of somatic mutations in hematopoietic stem cells and a precursor to myeloid malignancies, is not easily measured and is not routinely reported. TMN have an exceedingly poor prognosis, thus they may contribute to worsened overall survival, even in the setting of improved ovarian cancer-specific survival (i.e. improved PFS) in individuals treated with PARP inhibitors. Response to letter to the editor “AML and MDS associated with PARP inhibitor treatment of ovarian cancer”Gynecologic OncologyVol. 171PreviewWe would like to comment on the letter from Dr. Armstrong related to our recent article published in this journal [1]. We reported exploratory analyses that identified a subset of patients who achieved an exceptional response to rucaparib maintenance therapy within the ARIEL3 trial. With long-term outcome data now available for both the upfront and recurrent ovarian cancer settings, it is known that patients receiving PARPi therapy are at heightened risk of developing MDS/AML [2,3]. Indeed, the letter from Dr Armstrong provides a comprehensive and valuable summary of MDS/AML rates observed in PARPi maintenance studies (including ARIEL3). Full-Text PDF