Cadonilimab-associated hemophagocytic lymphohistiocytosis with relapse during glucocorticoid tapering: a case report

Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially life-threatening hyperinflammatory syndrome driven by excessive immune activation. Cadonilimab, a bispecific antibody targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), has shown antitumor activity in cervical cancer; however, the clinical phenotype and management of cadonilimab-associated HLH remain poorly defined. We describe cadonilimab-associated HLH in a 52-year-old woman with FIGO stage IVB cervical squamous cell carcinoma. She received three cycles of neoadjuvant albumin-bound paclitaxel plus nedaplatin with cadonilimab every 3 weeks and achieved a partial response, followed by definitive concurrent chemoradiotherapy with nedaplatin and two additional doses of cadonilimab. Approximately 2 weeks after the final cadonilimab dose, she developed intermittent high fever and progressive thrombocytopenia. Bone marrow aspiration showed hemophagocytosis. Laboratory testing revealed marked hyperferritinemia (peak, 11,409 ng/mL) and elevated soluble interleukin-2 receptor (IL-2R, 4,872 U/mL). Peripheral blood flow cytometry showed T-cell predominance, with T cells accounting for 96.03% of lymphocytes and a markedly inverted CD4/CD8 ratio (0.21). The patient fulfilled 5 of the 8 HLH-2004 criteria, and the H-score (274 points) indicated a high probability of HLH. Methylprednisolone 60 mg/day combined with intravenous immunoglobulin (IVIG) led to defervescence and hematologic recovery. HLH recurred when prednisone was tapered to 20 mg/day and resolved again after re-initiation of high-dose steroids followed by an extended taper (12 weeks in total). At the 20-month follow-up, the patient remained in complete remission of both HLH and cervical cancer. To our knowledge, this is the first reported case of cadonilimab-associated HLH. Clinicians should consider HLH in patients receiving cadonilimab who develop refractory fever and cytopenia, and a slow glucocorticoid taper may be required to prevent relapse.