Primary ovarian insufficiency secondary to chemotherapy with inotuzumab ozogamicin and other agents

Recent advances in targeted therapy with monoclonal antibodies have significantly improved outcomes for people with cancer, sometimes allowing patients to avoid ovotoxic agents altogether. The current understanding is that monoclonal antibody cancer therapies that are not targeted to ovarian antigens should not impact ovarian reserve or increase the risk of primary ovarian insufficiency (POI). We present a case of rapid onset POI in a 23-year-old patient following chemotherapy for relapse/refractory B-cell acute lymphoblastic leukemia with a monoclonal antibody drug-conjugate, inotuzumab ozogamicin, that targets CD22. She was also treated with intrathecal methotrexate, cytarabine, and vincristine which are typically considered low risk for ovotoxicity. She was ovulatory with an AMH of 1.0 ng/mL prior to treatment and 2 months later was found to have an undetectable AMH. The patient experienced a canceled fertility preservation cycle due to an absent response to gonadotropins during ovarian stimulation. Consideration should be given to potential gonadal effects of monoclonal antibody therapies that may not have previously been explored.