Supplementary Material for: Durvalumab induced immune thrombocytopenia (ITP) in patients with advanced cholangiocarcinoma undergoing yttrium-90-radioembolization.

Abstract
Introduction:
Immune thrombocytopenia (ITP) secondary to durvalumab, a Programmed Cell Death Ligand 1 (PD-L1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present two patients who developed ITP in patients with cholangiocarcinoma seen immediately post yttrium-90 radioembolization (Y90-RE) while on durvalumab based systemic therapy. We hypothesize given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and role for locoregional therapies, that often patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation. Comparison to other similar events of ITP in other disease types, e.g. in patients with non-small cell lung cancer and squamous cell carcinoma undergoing systemic immunotherapy alongside radiation therapy, is also presented.
Case Presentations:
Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in form of high dose steroids, intravenous immunoglobulins (IVIG), and durvalumab was discontinued. Only gemcitabine/cisplatin-based chemotherapy was continued thereafter. For one of the patients, it was recurrent and required longer courses of steroids as well as thrombopoietin receptor agonists (TRA).
Conclusion:
Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first line standard of care. Furthermore, it is not uncommon for patients to be receive Y90-RE to improved patient outcomes. This report highlights the development of ITP in two patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune mediated event is important allow for close monitoring of platelet counts to prevent any serious complications in patients getting this, and early intervention/management.