Recurrent endometrial carcinoma with immune-mediated thrombocytopenia following durvalumab: A case report

Abstract

The use of immune checkpoint inhibitors (ICIs) has expanded the therapeutic landscape for advanced or recurrent endometrial carcinoma. Durvalumab—a programmed death-ligand 1 (PD-L1) inhibitor—demonstrated clinical benefit in the 2023 DUO-E trial when combined with carboplatin and paclitaxel. Immune thrombocytopenia (ITP) is an uncommon but potentially life-threatening immune-related adverse event (irAE). A 73-year-old woman with recurrent endometrial carcinoma developed severe ITP after three cycles of paclitaxel, carboplatin, and durvalumab. Fourteen days after cycle 3 she presented with pyelonephritis, bacteremia, and acute disseminated intravascular coagulation (DIC). Despite infection control, her platelet count declined to 1 × 10³/μL, with epistaxis, hematuria, and melena. Suspecting ITP as an irAE, intravenous immunoglobulin (IVIG 10 g/day × 5 days) and high-dose intravenous prednisolone (1 mg/kg/day) were administered. Platelet counts improved gradually to 85 × 10³/μL by hospital day 32, and she was discharged on a steroid taper. This appears to be the first Japanese report of durvalumab-associated ITP in endometrial carcinoma. Clinicians should maintain a high index of suspicion for ITP when unexpected thrombocytopenia or bleeding occurs during durvalumab therapy and initiate prompt treatment.

Highlights

• •Severe immune-mediated thrombocytopenia occured after durvalumab with paclitaxel and carboplatin.
• •Intravenous immunoglobulin and high-dose steroids improved the profound thrombocytopenia.
• •Concomitant new-onset autoimmune type 1 diabetes indicated multiple immune-related adverse events.
• •Early recognition and prompt management are essential for hematologic immune-related adverse events.

1. Introduction

The incidence of endometrial carcinoma is increasing globally, with an estimated 420,368 new cases and 97,723 deaths reported in 2022 [1]. Immune checkpoint inhibitors (ICIs) have recently entered the treatment paradigm for advanced or recurrent disease. In 2023, the phase III DUO-E trial showed that adding durvalumab to first-line carboplatin–paclitaxel therapy improved progression-free survival, and a triplet regimen including olaparib provided additional benefit. Recent randomized clinical studies have consistently demonstrated that ICIs improve outcomes in advanced and recurrent endometrial carcinoma when added to standard chemotherapy. These benefits are most pronounced in tumors with mismatch-repair deficiency, reflecting their strong immunogenicity. Collectively, this expanding body of evidence supports incorporating PD-1/PD-L1 inhibitors into current treatment strategies.

Although durvalumab use in endometrial carcinoma is expanding, detailed descriptions of immune-related adverse events (irAEs) remain scarce. Immune thrombocytopenia (ITP) is a rare irAE, occurring in approximately 0.2–2.8 % of patients receiving ICIs [2,3,4]. Only a handful of durvalumab-related ITP cases have been described. This report, seemingly the first of a Japanese case, of severe ITP following durvalumab combination chemotherapy outlines the diagnostic and therapeutic challenges, and reviews the relevant literature.

2. Case Presentation

A 70-year-old woman (gravida 1, para 1) with a medical history of type 2 diabetes mellitus and hypertension presented to her local physician with abnormal vaginal bleeding. Her BMI was 29.4 kg/m². She was taking metformin 750 mg/day, linagliptin 5 mg/day, empagliflozin 25 mg/day, and amlodipine 5 mg/day, and she had no known drug allergies. Endometrial cytology suggested malignancy, and she was referred to hospital. Pelvic contrast-enhanced MRI indicated cervical invasion (clinical stage II). She underwent radical hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and omentectomy. Final pathology revealed grade 2 endometrioid adenocarcinoma, FIGO 2008 stage IIIB (pT3bN0M0). Immunohistochemistry demonstrated mismatch-repair proficiency with intact MLH1, MSH2, MSH6, and PMS2 expression, and p53 showed a wild-type staining pattern. Because comprehensive pelvic and para-aortic lymphadenectomy had been performed and negative nodal status was confirmed, the institutional practice—consistent with Japanese clinical guidelines—supported adjuvant chemotherapy without external-beam radiotherapy. Therefore, she received six cycles of paclitaxel (180 mg/m²) and carboplatin (AUC 6) without clinically significant myelosuppression.

Eighteen months after chemotherapy completion, contrast-enhanced PET identified a 2-cm abdominal mass suspicious for recurrence (Fig. 1). Exploratory surgery revealed diffuse peritoneal micrometastases; only a biopsy was performed, confirming recurrent disease. Systemic therapy with paclitaxel, carboplatin, and durvalumab (1120 mg every 3 weeks) was initiated. The patient was now aged 73. Fourteen days after the third cycle (cycle 3 day 14), she presented with fever (38.9 °C), epigastric pain, and dysuria. Laboratory tests showed white blood cell (WBC) count 11.9 × 10³/μL and C-reactive protein (CRP) 47.7 mg/L. Urinalysis revealed pyuria, and blood cultures grew Klebsiella oxytoca, confirming acute pyelonephritis with bacteremia. Broad-spectrum intravenous antibiotics were started.

Fig. 1.

A solitary recurrent lesion adjacent to the right obturator lymph node was detected on PET imaging.

Despite antimicrobial therapy, fever and inflammatory markers persisted. On hospital day 4, prothrombin time–international normalized ratio (PT-INR) was 1.21, fibrin/fibrinogen degradation products (FDP) 22.0 μg/mL, and platelet count 72 × 10³/μL, meeting criteria for acute disseminated intravascular coagulation (JAAM DIC score 5). Platelet count fell to 36 × 10³/μL on day 5, prompting transfusion of 10 units(approximately 200 mL) of platelets. By day 6 it had dropped to 3 × 10³/μL, with epistaxis and hematuria. Infection parameters improved under antibiotics (Fig. 2), yet thrombocytopenia worsened, reaching a nadir of 1 × 10³/μL on day 9, accompanied by melena. Hematology consultation raised suspicion for immune-mediated thrombocytopenia (ITP) as an irAE. Peripheral smear showed no schistocytes or blasts; WBC and hemoglobin were stable; antiplatelet antibody assays were negative; platelet-associated IgG (PAIgG) was elevated to 179.5 ng/10⁷ platelets. Bone marrow examination was deferred because of the bleeding risk at this critical platelet level. Treatment commenced on day 10 with intravenous immunoglobulin (IVIG 10 g/day for 5 days). High-dose intravenous prednisolone (50 mg/day, ∼1 mg/kg) was added on day 11. Platelet counts began to rise, reaching 6 × 10³/μL by day 17, permitting cessation of transfusions. By day 25, the count was 26 × 10³/μL, and prednisolone was tapered to 40 mg/day. Platelets continued to recover, and bleeding resolved. On day 32, the platelet count reached 85 × 10³/μL (Fig. 3).

Fig. 2.

Clinical course of body temperature and white blood cell (WBC) count after hospital admission.

The orange line represents body temperature (°C, left y-axis), and the blue line represents the WBC count (× 10³/μL, right y-axis). The patient developed disseminated intravascular coagulation (DIC) on day 4. Thrombomodulin therapy was initiated soon after DIC onset, and broad-spectrum antibiotics were administered throughout the early hospitalization period (yellow bar). Both body temperature and WBC count gradually decreased following antimicrobial therapy. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3.

Clinical course of platelet count and bleeding manifestations after hospital admission.

The red line shows the platelet count (× 10³/μL, y axis) over time. The patient developed severe thrombocytopenia with nadir platelet count of 1 × 10³/μL on day 9, accompanied by nosebleed, hematuria, and melena (indicated by the colored ovals). Platelet transfusions were administered daily (orange triangles). Immune thrombocytopenia (ITP) was suspected (yellow arrow), and intravenous immunoglobulin (IVIG 10 g/day for 5 days; green bar) and high-dose prednisolone (PSL 50 mg/day followed by 40 mg/day; blue bars) were initiated. Platelet counts gradually recovered after initiation of immunosuppressive therapy. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

During hospitalization, poor glycaemic control was observed, necessitating insulin therapy. Additionally, ketoacidosis was noted and, given the presence of GAD antibodies, the patient was diagnosed with ICI-induced autoimmune type 1 diabetes. The patient was discharged on hospital day 35 in good condition. Following discharge, prednisolone was tapered by 10 mg increments until steroid withdrawal was achieved.

Following steroid withdrawal, treatment with tri-weekly paclitaxel and carboplatin combination therapy was resumed, with response ranging from partial to stable disease.

3. Discussion

Durvalumab-related ITP is exceedingly rare; this report appears to be the first in a patient with endometrial carcinoma in Japan. ITP remains an uncommon irAE associated with ICIs, and only a limited number of durvalumab-related cases have been reported [5]. Median onset for PD-L1 inhibitor–associated ITP is 21 days (range 13–131) [6]. In the DUO-E trial, one ITP case occurred 77 days after first durvalumab dose [7]. The patient developed ITP approximately 65 days after initiation, consistent with reported timelines. The occurrence of irAEs has been associated with improved overall and progression-free survival [8,9]. Multiple irAEs—seen in 10–30 % of ICI-treated patients—may correlate with even better outcomes [10,11]. The patient developed both ITP and autoimmune diabetes, suggesting a robust immune activation; however, hematologic irAEs such as ITP can be severe and are linked to lower rates of survival [12]. Rechallenge with ICIs carries a 25 % risk of irAE recurrence, rising to 33 % for hematologic events [13,14]. With other solid tumors, there have been reports of successful re-administration of ICI to patients who developed ITP following initial ICI treatment [15].Therefore, resuming durvalumab in this patient had to balance potential antitumor benefit against significant risk. Diagnosis of ITP in the ICI setting requires exclusion of alternative causes, including marrow failure, drug-induced thrombocytopenia, infection, and thrombotic microangiopathy. An elevated PAIgG level, persistent thrombocytopenia despite infection control, and response to IVIG and corticosteroids supported the diagnosis. Bone marrow biopsy was deferred because of extreme bleeding risk; future guidelines should address safe diagnostic strategies where there is profound thrombocytopenia.

4. Conclusion

This report concerns a rare case of severe immune-mediated thrombocytopenia following durvalumab in a patient with recurrent endometrial carcinoma. Although ITP is uncommon among irAEs, it carries a high risk of life-threatening bleeding. Clinicians should promptly evaluate unexpected thrombocytopenia or bleeding during durvalumab therapy, initiate early immunosuppressive treatment, and carefully weigh the risks of ICI rechallenge.

Contributors

Ami Sakakibara contributed to patient care, conception of the case report, acquiring and interpreting the data, drafting the manuscript, undertaking the literature review, and revising the article critically for important intellectual content.

Shimpei Nagai contributed to patient care, drafting the manuscript, and revising the article critically for important intellectual content.

Terumi Shirane contributed to patient care and interpreting the data.

Tomomi Sakai contributed to the conception of the case report and acquiring the data.

Yoko Fujioka contributed to the conception of the case report and acquiring the data.

Makiko Hino contributed to the conception of the case report and acquiring the data.

Yoshihisa Hattori contributed to revising the article critically for important intellectual content.

Takashi Kurahashi contributed to revising the article critically for important intellectual content.

All authors approved the final submitted manuscript.

Patient consent

Written informed consent was obtained from the patient for the publication of the case report and accompanying images.

Provenance and peer review

This article was not commissioned and was peer reviewed.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of competing interest

The authors declare that they have no competing interest regarding the publication of this case report.