A Diagnostic of Acquired Hemophilia Following PD1/PDL1 Inhibitors in Advanced Melanoma: The Experience of Two Patients and a Literature Review

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the development of specific autoantibodies against factor VIII (FVIII). Immunotherapy is a recent therapeutic option that targets the patient's self-tolerance against tumor cells. Because therapeutic effects of the immune checkpoint inhibitors (ICIs) are mediated by enhancing the immune response to restore antitumor immunity, autoimmune-related adverse effects can be seen in up to 80% of patients during treatment and after treatment. A rare hematologic ICIs-related adverse event is AHA. Hereafter we report two cases of AHA developed during anti-PD-1 immunotherapy for advanced melanoma: one secondary to treatment with nivolumab and one secondary to pembrolizumab. Both patients were treated with activated FVII (Novoseven^®, Novo Nordisk, Bagsværd, Denmark) as hemostatic treatment combined with the eradication of antibodies anti-FVIII obtained with rituximab. In the last few years these drugs have significantly improved the therapeutic armamentarium for the management of AHA. Indeed, while FVIIa has proven to be an effective and safe tool for the treatment of acute bleeding related to FVIII autoantibodies, rituximab is a promising alternative for the autoantibodies' elimination and the restoration of normal hemostasis. Our finding supports the use of this combination even in AHA secondary to ICIs treatment.