Case Report: Successful rechallenge of cadonilimab-induced cystitis, adrenal insufficiency, and diabetic ketoacidosis in a patient with metastatic gastric-type endocervical adenocarcinoma

Background: Gastric-type endocervical adenocarcinoma (GEA) is an aggressive, HPV-independent malignancy with a poor prognosis. Cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, has shown promising efficacy in advanced cervical cancer but may increase the risk of immune-related adverse events (irAEs), including rare multiorgan involvement. Reports of sequential, multiorgan irAEs involving the urinary tract and endocrine system following cadonilimab therapy, as well as subsequent successful rechallenge, are exceedingly rare. Case presentation: A 70-year-old female with stage IVB GEA developed concurrent irAEs nine months after initiating first-line chemotherapy combined with cadonilimab and bevacizumab. She initially presented with urinary frequency, urgency, and fatigue. Investigations revealed grade II immune-related cystitis (based on imaging and persistently negative urine cultures) and concurrent grade III adrenal insufficiency (AI) with low serum cortisol and inappropriately normal ACTH levels. Immunotherapy was temporarily suspended, and she commenced hydrocortisone replacement therapy, resulting in symptom amelioration. After symptom resolution, cadonilimab was rechallenged on August 16, 2025. Four months later, she developed diabetic ketoacidosis (DKA) and received a diagnosis of grade IV immune-related diabetes mellitus (DM), requiring insulin therapy. After metabolic stabilization, cadonilimab was rechallenged again. As of the last follow-up, the patient had received 24 cycles of cadonilimab, achieving a progression-free survival (PFS) of 17 months with no recurrence of prior irAEs. Conclusion: This case highlights the rare but possible occurrence of sequential, multiorgan irAEs, including cystitis, AI, and DKA, following cadonilimab therapy. This case underscores the importance of multidisciplinary collaboration, vigilant monitoring, and individualized rechallenge decisions in managing complex irAEs. Importantly, it demonstrates that immunotherapy rechallenge can be feasible and provide sustained clinical benefit in selected patients with advanced GEA after resolution of severe irAEs.