Frontiers in Immunology · Published 2026-08-04 · DOI 10.3389/fimmu.2026.1908239
Qiqi Chen, Xiaojing Song, Ming Zhang, Hongxia Niu, Wei Guo
BackgroundIvonescimab is a PD-1/VEGF bispecific antibody that combines immune checkpoint blockade with anti-angiogenic activity. As PD-1/VEGF-directed regimens enter routine solid-tumor care, rare toxicities at the interface of immune activation, endothelial injury, and thrombotic microangiopathy require careful case-level characterization.Case presentationA 63-year-old man with stage IVB lung adenocarcinoma (cT1bN2M1c, with multiple extrathoracic rib metastases) received an ivonescimab-containing combination regimen consisting of three cycles of ivonescimab plus nab-paclitaxel and cisplatin, followed by chemotherapy alone after partial response. He developed fever, severe cholestatic liver injury, and KDIGO stage 3 acute kidney injury requiring temporary continuous renal replacement therapy. Serum creatinine peaked at 767 µmol/L and subsequently normalized. Evolving anemia, thrombocytopenia, schistocytes, Coombs-negative hemolysis, and organ injury prompted evaluation for thrombotic microangiopathy. ADAMTS13 activity was 8.87% with a functional inhibitor of 1.8 BU/mL, confirming acquired immune-mediated thrombotic thrombocytopenic purpura. The PLASMIC score was 5, reflecting intermediate clinical probability because active malignancy and MCV >90 fL lowered the score; definitive diagnosis therefore depended on ADAMTS13 testing. Treatment included corticosteroids, 10 sessions of DPMAS/TPE support with transition to FFP-based plasma exchange once iTTP was recognized, and rituximab 500 mg weekly from April 17 to May 8, 2026. Caplacizumab was not used because it was unavailable locally. No platelet transfusions were administered; red blood cells and plasma were transfused as clinically indicated. ADAMTS13 activity increased to 23.82% and inhibitor titer decreased to 0.85 BU/mL on the available follow-up test, but serial ADAMTS13 and complement measurements were not available. The patient had biochemical improvement and normalization of renal function.ConclusionThis case highlights ADAMTS13 inhibitor-positive iTTP as a rare, actionable toxicity after ivonescimab-containing chemoimmunotherapy rather than proof of ivonescimab as the sole causal agent. The renal phenotype should be framed as severe but reversible AKI rather than dialysis-dependent renal failure. In patients receiving PD-1/VEGF-directed combination therapy, thrombocytopenia with microangiopathic hemolysis and organ injury should trigger smear review, PLASMIC scoring, urgent ADAMTS13 testing, and early mechanism-directed therapy.
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Chen, Q., Song, X., Zhang, M., et al. (2026). Acquired immune-mediated thrombotic thrombocytopenic purpura with severe cholestatic liver injury and reversible acute kidney injury after ivonescimab-containing chemoimmunotherapy: a case report and literature review. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2026.1908239