---
title: "Cadonilimab-associated multi-organ damage: case report overview and missing details"
id: "frontiers-in-immunology-14-case-report-severe-multi-organ-damage-induced-by-cadonilimab-mechanism"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-case-report-severe-multi-organ-damage-induced-by-cadonilimab-mechanism"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1961670"
published_at: "2026-10-01T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Cadonilimab-associated multi-organ damage: case report overview and missing details
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-case-report-severe-multi-organ-damage-induced-by-cadonilimab-mechanism
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1961670)
- **Published At:** 2026-10-01T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source provided was a Frontiers in Immunology case report titled indicating **cadonilimab** caused severe **multi-organ damage**, with a focus on mechanism investigation and management strategies. - The publicly shared page content in the provided source contained only website navigation and journal metadata; the full article text and case details were not included in the supplied source. - Key clinical details — patient demographics, timeline of exposure, organ systems affected, laboratory and imaging findings, histopathology, specific mechanistic data, treatments administered, and clinical outcomes — were not reported in the supplied source. - The title implies two main components: an exploration of the **mechanism** of cadonilimab-induced toxicity and proposed **management strategies**, but the supplied content did not report methods, experimental data, or guidance details. - Because the source text was incomplete, no specific recommendations, numerical data, or case outcomes can be restated; any clinical inference beyond the title would be speculative and was therefore omitted. - The rewritten summary therefore documents what is known (title, journal), enumerates expected sections that a full case report would include, and highlights that all substantive clinical information was not available in the provided source.
## Clinical Analysis & Structured Key Points
Frontiers | Case Report: Severe multi-organ damage induced by cadonilimab: mechanism investigation and management strategies CASE REPORT article Front. Immunol. , 01 October 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1961670 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Part of a Research Topic The role of immunotherapy in cancer therapy and its challenges - volume II Submission open 31k views 20 articles Editor & Reviewers Edited by J J Jeffrey J Pu Reviewed by R I Rania I.M. Almoselhy F M Fariba Mahmoodpoor Outline Figures and Tables Figure 1 View in article Figure 2 View in article Table 1 Changes in laboratory indicators. View in article Table 2 Integrated clinical timeline of treatment exposure, manifestations, investigations, management, and outcomes. View in article Table 3 Summary of the incidence rates of immune-related adverse reactions of different ICIs ( 12 , 13 , 20 – 22 )(%). View in article Table 4 Clinical trials related to cadonilimab. View in article CASE REPORT article Front. Immunol. , 01 October 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1961670 Case Report: Severe multi-organ damage induced by cadonilimab: mechanism investigation and management strategies B S Bin Shan 1 † R Y Ruixia Yang 2 † Y P Yi Peng 1 M L Mengjiao Li 1 * 1. Department of Pharmacy, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China 2. Department of Pharmacy, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China Article metrics View details Abstract Most immune checkpoint inhibitors currently used in clinical practice, such as programmed cell death protein 1/programmed death ligand 1 (PD 1/PD L1) inhibitors and cytotoxic T lymphocyte antigen 4 (CTLA 4) inhibitors, are monospecific antibodies acting on a single target. In contrast, bispecific antibodies (BsAbs) contain an additional specific antigen binding site, enabling dual signaling pathway blockade and more potent inhibition of tumor growth. In June 2022, the first PD 1/CTLA 4 BsAb cadonilimab (AK104) was approved by the National Medical Products Administration of China for the treatment of cervical cancer and gastric or gastroesophageal junction adenocarcinoma. Owing to its recent market approval, only a limited number of studies have reported immune related adverse events (irAEs) associated with this drug, involving the skin, gastrointestinal tract, liver, and other organs. Thus far, no case of cadonilimab related multi organ injury has been described. In this article, we report the first case of severe immune related multi organ and endocrine system injury induced by cadonilimab in the treatment of cervical cancer. In addition, we conducted a retrospective literature analysis comparing the adverse drug reaction (ADR) profiles of immune checkpoint inhibitor monospecific antibodies and BsAbs. The aim of this analysis was to provide a reference for the rational use of cadonilimab. Early recognition of irAEs, identification of risk factors, regular monitoring, use of corticosteroids, and supportive care are critical for improving clinical outcomes. It should be emphasized that the oncologic benefits of BsAb therapy generally outweigh the risks of ADRs, and treatment should not be discontinued or delayed except in rare circumstances (e.g., multi organ failure). In case of ADR occurrence, familiarity of the healthcare professionals with the relevant irAEs is essential to facilitate effective diagnosis and appropriate management of this increasingly common pattern of multi organ injury. 1 Introduction Immunotherapy represents the most promising systemic modality for the treatment of cancer and is critically important for improving therapeutic outcomes. The occurrence and progression of malignant tumors involve complex pathohistological and molecular biological mechanisms, and monoclonal antibodies targeting a single antigen are often insufficient to achieve adequate therapeutic effects. This has led to the development of bispecific antibodies (BsAbs), which are artificial antibodies generated through technologies such as cell fusion, recombinant DNA, and protein engineering. BsAbs can specifically bind to two different antigens or two distinct epitopes of the same antigen either simultaneously or sequentially, introducing a new era of tumor immunotherapy ( 1 , 2 ). Cadonilimab is the first dual immune checkpoint inhibitor (ICI) for tumor treatment entirely developed and approved in China. This agent simultaneously targets two immune checkpoints, namely programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), enabling preferential binding to tumor-infiltrating lymphocytes ( 3 ). The results of clinical trials with this drug have demonstrated novel breakthroughs in the treatment of advanced cervical cancer ( 4 ), gastric cancer with low or negative programmed death ligand 1 (PD L1) expression ( 5 ), and lung cancer (AK104 IIT 018). ICIs block T cell negative regulatory signals, relieve immunosuppression, and enhance T cell antitumor effects. However, they may also abnormally potentiate immune responses, leading to disruption of immune tolerance and immune-related adverse events (irAEs) that affect normal tissues. Among these, irAEs involving the skin, gastrointestinal tract, endocrine system, lungs, and musculoskeletal system are relatively common ( 6 ). Common adverse drug reactions (ADRs) of BsAbs in antitumor therapy include cytokine release syndrome, neurotoxicity, infection, and hematologic and lymphatic toxicities ( 7 ). According to the literature, the combination of PD 1 and CTLA 4 antibodies is associated with a marked increase in grade 3–4 ADRs without necessarily improving clinical benefit ( 8 ). Although cadonilimab targets two immune checkpoints simultaneously, its safety profile in the process of enhancing immune killing effects warrants in depth investigation. Thus far, no case of severe multi organ injury induced by cadonilimab has been reported. In this article, we focus on the underlying mechanisms and strategies for the management of multi organ injury. The aim is to highlight that close monitoring of multi system organ function is essential when using BsAbs in clinical practice. Moreover, we propose that novel biomarkers should be utilized to improve early diagnosis and prognosis of multi organ injury, thereby enhancing the safety of this therapeutic approach. 2 Case presentation In February 2022, a 53-year-old female patient presented with irregular vaginal bleeding without obvious cause. Human papillomavirus (HPV) testing was positive for HPV-16 and HPV-50. Cervical biopsy pathology showed non-keratinizing squamous cell carcinoma. On February 18, 2022, pelvic magnetic resonance imaging (MRI) revealed an irregular mass with isointense T1 and slightly hyperintense T2 signals in the cervix, measuring approximately 4.9 cm × 4.8 cm, consistent with cervical cancer. The patient was diagnosed with stage III C1r squamous cell carcinoma of the cervix and received two cycles of concurrent radiotherapy with nedaplatin and cisplatin, plus nimotuzumab targeted therapy. Subsequently, she received three cycles of albumin-bound paclitaxel plus cisplatin combined with nimotuzumab, with the last treatment completed in July 2022. The treatment response was evaluated as partial response. On December 4, 2023, contrast-enhanced computed tomography of the neck, chest, and abdomen suggested possible enlarged lymph nodes. On December 18, 2023, lymph node biopsy showed metastatic squamous cell carcinoma, consistent with cervical origin based on the patient’s history. On December 30, 2023, brain MRI showed a left maxillary sinus cyst, with no abnormalities on cranial MRI; pathological analysis revealed a small amount of squamous cell carcinoma, also considered of cervical origin. Subsequently, the patient was treated with a TP regimen: albumin-bound paclitaxel 0.3 g (January 2, 2024) plus cisplatin 40 mg (January 2–4, 2024) plus cadonilimab 500 mg (January 2, 2024). On January 13, 2024, microsatellite instability testing of cervical tissue showed a microsatellite stable status. On January 16, 2024, PD L1 testing showed a Tumor cell Proportion Score of 45% and a Combined Positive Score of 46%. Following discharge, the patient reported intermittent wheezing and chest tightness worsening over 1 week, with occasional cough and sputum production. On January 31, 2024, she was admitted to our hospital primarily due to wheezing for more than half a month, worsening for 1 week, after radiotherapy and chemotherapy for cervical cancer with mediastinal lymph node metastasis. 2.1 Diagnosis and treatment On January 31, 2024, laboratory examinations yielded critical results: cardiac troponin I (cTnI) 0.779 μg·L −1 ; C-reactive protein 11.80 mg·L −1 ; liver function, myocardial enzymes, and electrolytes: sodium 138.0 mmol·L −1 , potassium 3.90 mmol·L −1 , alanine aminotransferase (ALT) 427.0 U·L −1 , aspartate aminotransferase (AST) 538.0 U·L −1 , total bilirubin 9.1 μmol·L −1 , direct bilirubin 3.8 μmol·L −1 , glucose 6.82 mmol·L −1 , creatine kinase (CK) 6,867.4 U·L −1 , creatine kinase MB (CK MB) 195.55 U·L −1 , lactate dehydrogenase 1,601 U·L −1 , α hydroxybutyrate dehydrogenase 1,430.7 U·L −1 ; thyroid function tests: thyroid stimulating hormone 0.107 mIU·L −1 , triiodothyronine 1.63 nmol·L −1 , thyroxine 190.05 nmol·L −1 , pituitary function was normal. The patient reported palpitations and shortness of breath with an oxygen saturation of 99%. Oxygen was administered via a nasal cannula, and palpitations improved. Electrocardiography (ECG) showed sinus tachycardia (121 bpm). Transthoracic echocardiography at rest revealed mild tricuspid regurgitation, minimal pericardial effusion, normal left ventricular systolic function, and reduced diastolic function. Initial diagnoses included grade 2 myocarditis, grade 3 liver injury, grade 1 pneumonitis, and grade 1 hyperthyroidism. Treatment was initiated with methylprednisolone sodium succinate 120 mg intravenously once daily (ivgtt qd) from January 31 to February 7, 2024, as pulse therapy; the treatment also included magnesium isoglycyrrhizinate 200 mg ivgtt qd from January 31 to February 8, plus polyene phosphatidylcholine injection 465 mg ivgtt qd from February 1 to February 8 for liver protection; and ceftriaxone sodium 2 g ivgtt qd from January 31 to February 8 for anti infection. On February 1, 2024, the patient reported relief of chest tightness and wheezing. On February 2 and February 7, the patient underwent further examination of liver function, renal function, myocardial enzymes, N terminal pro B type natriuretic peptide, and cTnI levels ( Table 1 ). Methylprednisolone was tapered to 80 mg ivgtt qd from February 7 to February 10. The symptoms improved markedly, and the levels of liver enzymes and myocardial enzymes decreased, indicating effective treatment. She was discharged on February 11, 2024, receiving oral methylprednisolone 64 mg once daily. Table 1 Laboratory indicator 31-01-2024 01-02-2024 02-02-2024 04-02-2024 07-02-2024 23-04-2024 Cardiac Troponin I(μg·L -1 ) 0.779 0.459 0.469 0.454 0.259 0.012 C-reactive protein(g·L -1 ) 11.8 / / 1. 19 / / Alanine Aminotransferase(U·L -1 ) 427 348 276 222.2 126 13.9 Aspartate Aminotransferase(L -1 ) 538 282 135.3 87.3 49.6 17.2 Total Bilirubin(μmol·L -1 ) 9.1 / / 6.6 7.2 / Direct Bilirubin(mol·L -1 ) 3.8 / / 3.6 3.3 / Creatine Kinase(U·L -1 ) 6 867.4 3 418 1 676.5 1 165.8 617.4 / Creatine kinase-MB(U·L -1 ) 195.55 83.13 45.36 45.4 49.91 / Lactate dehydrogenase(U·L -1 ) 1 601 1 309 1 110 1 037 779 / Hydroxybutyrate-dehydrogenase(U·L -1 ) 1 430.7 1 235.1 1 094.1 1 011.3 744.5 / Thyroid Stimulating Hormone(mIU·L -1 ) 0.107 / / 0.059 / 1.342 Triiodothyronine(nmol·L -1 ) 1.63 / / 1.02 / 2.25 Thyroxine(mo1·L -1 ) 1 90.05 / / 168.64 / 116.35 N-terminal pro-brain natriuretic peptide(ng·L -1 ) / 159 245 / / 26.9 Changes in laboratory indicators. ”/”indicates no data. 2.2 Post-discharge follow-up On February 8, 2024, chest computed tomography showed enlarged mediastinal lymph nodes, with no significant change observed compared with February 1, 2024. The patient was discharged on February 11 receiving oral methylprednisolone 64 mg once daily. After discharge, the dose was reduced by 8 mg every 5 days (February 15, February 20, February 25, March 1, March 6, March 11, and March 16). It reached 8 mg/day on March 16, was further reduced to 4 mg/day on March 22, and was discontinued on March 27. Myocardial enzymes, liver enzymes, thyroid function, and blood glucose were monitored throughout the taper. Cadonilimab was permanently discontinued. On April 23, 2024, anticancer therapy was changed to albumin-bound paclitaxel 0.3 g plus bevacizumab 400 mg. Brain and abdominal MRI on April 26 showed multiple small hepatic cysts and left maxillary sinus inflammation, with no intracranial abnormality; the tumor response remained a partial response. At the 6-month follow-up after discharge, the cardiac injury, liver injury, and endocrine toxicity had resolved, the relevant laboratory indices had returned to their reference ranges ( Table 1 ), and no residual symptoms, complications, or need for additional immunosuppressive treatment were reported. The patient remained under oncology follow-up while receiving the revised anticancer regimen. The chronological relationship among drug exposure, symptoms, investigations, treatment, and outcomes is summarized in Table 2 and Figure 1 . Table 2 Date Anticancer/immune therapy Clinical signs and symptoms Relevant tests/laboratory findings Management and outcome 18 Feb 2022 Diagnosis; no immunotherapy Irregular vaginal bleeding Pelvic MRI: 4.9 × 4.8 cm cervical mass; biopsy: non-keratinizing squamous cell carcinoma; stage IIIC1r Cervical cancer diagnosed Feb–Jul 2022 Concurrent radiotherapy + nedaplatin/cisplatin + nimotuzumab; then nab-paclitaxel/cisplatin + nimotuzumab — Imaging response assessment Partial response 4–30 Dec 2023 — Recurrent disease suspected Enlarged lymph nodes; biopsy confirmed metastatic squamous cell carcinoma of cervical origin; brain MRI without intracranial abnormality Systemic treatment planned 2–4 Jan 2024 Nab-paclitaxel 0.3 g (2 Jan) + cisplatin 40 mg/day (2–4 Jan) + cadonilimab 500 mg (2 Jan) Initially no acute symptoms MSS; PD-L1 TPS 45%, CPS 46% Single documented cadonilimab administration Mid–31 Jan 2024 Cadonilimab not re-administered Intermittent dyspnea and chest tightness for >2 weeks, worsening for 1 week; palpitations; occasional cough/sputum ECG: sinus tachycardia 121 bpm; cTnI 0.779 μg/L; CK 6,867.4 U/L; CK-MB 195.55 U/L; ALT 427 U/L; AST 538 U/L; TSH 0.107 mIU/L; echocardiography: minimal pericardial effusion with preserved LV systolic function G2 myocarditis, G3 liver injury, G1 pneumonitis, and G1 hyperthyroidism diagnosed 31 Jan–11 Feb 2024 Cadonilimab withheld Chest tightness and dyspnea improved Progressive decline in cardiac and hepatic injury markers ( Table 1 ) IV methylprednisolone 120 mg/day (31 Jan–7 Feb), then 80 mg/day (7–10 Feb); liver-supportive therapy and ceftriaxone; discharged 11 Feb on oral methylprednisolone 64 mg/day 15 Feb–27 Mar 2024 No further cadonilimab No recurrent reported cardiopulmonary symptoms Serial cardiac enzymes, liver enzymes, thyroid function, and glucose monitored Oral methylprednisolone reduced by 8 mg every 5 days; 8 mg on 16 Mar, 4 mg on 22 Mar, discontinued 27 Mar 23 Apr–Aug 2024 Nab-paclitaxel + bevacizumab; cadonilimab permanently discontinued No residual symptoms or complications reported at 6 months Cardiac, hepatic, and endocrine laboratory indices returned to normal ranges; imaging showed maintained partial response Toxicities resolved without additional immunosuppression; ongoing oncology follow-up Integrated clinical timeline of treatment exposure, manifestations, investigations, management, and outcomes. Figure 1 Chronology of anticancer treatment, onset of cadonilimab-associated multi-organ immune-related adverse events, management, and clinical outcome. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; cTnI, cardiac troponin I; G, grade; irAE, immune-related adverse event; PR, partial response; TSH, thyroid-stimulating hormone. 2.3 Ethics approval and consent to participate The study was approved by the Clinical Research Ethics Committee of the Fourth Hospital of Hebei Medical University (approval number: 2023-126-K92). The patient was informed regarding the study protocol and provided written informed consent to participate in the study. 3 Discussion 3.1 Characteristics of ICI-induced multi-organ injury ICI-related cardiotoxicity manifests variably as myocarditis, arrhythmias, conduction disorders, and myocardial infarction. ICI-associated myocarditis is a rare (incidence ≤1%) but severe ADR with a median onset of 17–65 days post-treatment ( 9 – 12 ) and a high mortality rate of 38% ( 12 ). The patient had no prior cardiovascular disease, while baseline cardiac markers and ECG were normal. She developed intermittent wheezing and chest tightness 14 days after receiving TP plus cadonilimab, with cTnI, CK, and CK-MB levels markedly exceeding the upper limit of normal (ULN); the onset of symptoms was earlier than that previously reported in the literature. ECG showed no features of acute coronary syndrome; together with other cardiac markers, the findings met the diagnostic criteria for “suspected myocarditis”, graded as G2 myocardial injury ( 9 – 11 , 13 – 15 ). Immunotherapy-mediated hepatotoxicity (IMH) typically occurs within 4–12 weeks after the first treatment and is the third most common irAE. With monotherapy, elevation of ALT/AST levels occurs in 3–9% of patients receiving CTLA-4 inhibitors, 1.5–5% receiving PD-1 inhibitors, and 3% receiving PD-L1 inhibitors, with grade 3 or 4 severe hepatotoxicity accounting for approximately 1% of cases ( 16 ). The onset in this case was earlier than that reported in the literature. According to the Common Terminology Criteria for Adverse Events (CTCAE) version 6 ( 17 ), the ALT/AST levels of this patient were 5–10-fold higher than the ULN after treatment with cadonilimab, and this condition was classified as grade 3 liver injury (ALT or AST > 5 × ULN to < 20 × ULN). Based on the Chinese Guidelines for the Diagnosis and Management of Drug-Induced Liver Injury (2023 Edition) ( 18 ), the Roussel Uclaf Causality Assessment Method scale score was 7, indicating that the liver injury was likely induced by the drug. The R value was 3.8 (2 < R < 5), consistent with a mixed clinical phenotype. Next, the patient received albumin-bound paclitaxel without liver injury, temporarily excluding paclitaxel as the cause. ICI-related hyperthyroidism typically occurs within 2–6 weeks after treatment ( 13 , 19 ). The patient had normal baseline thyroid function and exhibited free thyroxine levels markedly exceeding the ULN after receiving TP plus cadonilimab; the onset was consistent with that previously reported in the literature. According to CTCAE version 6 ( 17 ), the thyroid toxicity was grade 2 (symptomatic; thyroid hormone replacement therapy indicated). Comparisons of ADR incidence among patients receiving PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, and PD-1/CTLA-4 BsAb combination therapy are summarized in Table 3 ( 12 , 13 , 20 – 22 ). A meta-analysis showed that dual ICIs (PD-1 plus CTLA-4 inhibitors) did not increase overall cardiovascular adverse events compared with monotherapy; nonetheless, the incidence of myocarditis was significantly higher in the combination group ( 12 ). According to these studies, CTLA-4 inhibitors generally increase the incidence of IMH more than PD-1/PD-L1 inhibitors, and ICI combination therapy further increases the risk of IMH. Addit
## Related Clinical Research

- [Neoadjuvant serplulimab plus chemotherapy achieves high MPR in locally advanced squamous NSCLC](https://medichelpline.com/clinical-feed/frontiers-in-immunology-2-neoadjuvant-serplulimab-combined-with-chemotherapy-in-locally-advanced-driver.md)
- [Editorial placeholder: Innovative therapeutic approaches for complex cancers — source content miss](https://medichelpline.com/clinical-feed/frontiers-in-immunology-12-editorial-innovative-therapeutic-approaches-for-complex-cancers-exploring-new.md)
- [SIRT6 modulation of Nrf2 enhances cisplatin response in lung cancer models](https://medichelpline.com/clinical-feed/pubmed-42727479.md) (DOI: 10.1016/j.bbrc.2026.154563)
- [SCRMP drives cisplatin resistance in small cell lung cancer via CSNK2B SUMOylation and enhanced DN](https://medichelpline.com/clinical-feed/pubmed-42777084.md) (DOI: 10.1126/scitranslmed.aea5653)
- [PD-L1 expression and survival in unresectable or recurrent gastric cancer treated with first-line](https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-pd-l1-expression-and-survival-in-unresectable-recurrent-gastric-cancer-treated.md)

## Navigation
- [← Back to Infectious Disease Feed](https://medichelpline.com/clinical-feed/infectious-disease.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.