Durvalumab-Induced Immune Thrombocytopenia in Patients with Advanced Cholangiocarcinoma Undergoing Yttrium-90 Radioembolization

Abstract

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications.

Case presentation: 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 the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists.

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 receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs.

Keywords: Cholangiocarcinoma; Durvalumab; Immune thrombocytopenia; Yttrium-90.

Fig. 1.

a Axial delayed arterial phase imaging showing a large, heterogeneously enhancing right hepatic mass. b Coronal T2-weighted MRI demonstrating heterogeneously increased signal intensity with associated capsular retraction, consistent with biopsy-proven cholangiocarcinoma.

Fig. 2.

a Axial portal venous phase imaging post-lobar Y90, with partial response and nodular enhancement consistent with viable tumor. b Coronal portal venous phase imaging demonstrating partial response post-lobar Y90.

Fig. 3.

Changes in the patient’s platelet count over the course of her treatment. Arrows on the graph mark the specific time points when the patient received various treatments, including durvalumab, combination chemotherapy (gemcitabine/cisplatin), Y90 radioembolization, and steroids.

Fig. 4.

Changes in the patient’s platelet count over the course of his treatment. Arrows on the graph mark the specific time points when the patient received various treatments, including Durvalumab, combination chemotherapy (gemcitabine/cisplatin), Y90 radioembolization, FOLFOX, Gem/Nab-p, thrombopoietin receptor agonist (TRA), intravenous immunoglobulin (IVIG), and steroids.

Fig. 5.

a Axial portal venous phase imaging 5 months post-thermal ablation. Ablation cavity noted with linear tract from percutaneous approach. b Arterial subtraction imaging showing irregular peripheral enhancement of the ablation cavity (arrows), concerning for recurrent disease given associated increase in CA 19-9.

Fig. 6.

a Axial portal venous phase MRI 6 weeks post-ablative Y90 treatment, with expected perfusional changes and no definite residual tumor enhancement. b Axial portal venous phase CT 9 weeks post-Y90 with continued evolution of posttreatment effect.