Efgartigimod for immune checkpoint inhibitor induced polyradiculoneuropathy and cardiomyopathy: A case report

Introduction

Immune checkpoint inhibitors (ICIs) have markedly improved clinical outcomes across a range of malignancies (1). By inhibiting signal transduction pathways like programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein (CTLA)-4, ICIs enhance the T-cell-mediated anti-tumor immune response, leading to durable remissions and survival advantages, particularly in cancers historically considered refractory, including metastatic melanoma and non-small cell lung cancer (1). Despite their efficacy, ICIs are associated with immune-related adverse events (irAEs), which may involve nearly any organ system.

IrAEs are common, occurring in ~90% of patients receiving anti-CTLA-4 therapy and 70% of those treated with anti-PD-1/PD-L1 agents (2). Although less frequent than dermatologic or gastrointestinal irAEs, neurological irAEs, affecting ~1-3% of patients, are particularly concerning due to their potential severity and risk of long-term disability (3). Among these, polyradiculoneuropathy (PRN) and myocarditis represent severe manifestations of neurological and cardiac irAEs, respectively. Although rare, these events can be life-threatening: Severe PRN has been associated with mortality rates of up to 60% (4,5), while ICI-related myocarditis has a fatality rate approaching 50% (6). The pathogenesis of irAE has been reported to involve complex immune dysregulation, including autoreactive T-cell activation and cellular/humoral immune-mediated tissue damage (3).

The management of severe or refractory irAEs remains a significant clinical challenge. First-line treatment typically consists of high-dose corticosteroids combined with supportive care (1). However, second-line therapies such as intravenous immunoglobulin (IVIG) or plasmapheresis demonstrate variable efficacy and substantial mortality (4,5). This highlights the urgent need for novel therapeutic strategies targeting specific immune pathways. Efgartigimod, a neonatal Fc receptor (FcRn) antagonist, enhances the degradation of pathogenic IgG autoantibodies. Its established efficacy and favorable safety profile in antibody-mediated disorders like generalized myasthenia gravis (7) suggest its potential utility in treating refractory, antibody-mediated irAEs (8).

The present case report describes marked neurological and cardiac improvement in a patient with metastatic pancreatic cancer who developed severe, refractory ICI-induced PRN and myocarditis following treatment with efgartigimod. The findings underscore FcRn blockade as a promising therapeutic approach for managing life-threatening, treatment-resistant irAEs.

Case report

Clinical presentation

A 63-year-old female was diagnosed with pancreatic ductal adenocarcinoma in December 2023 at Zhongshan Hospital, Fudan University (Shanghai, China). The patient received first-line chemotherapy with 1.4 g cytarabine plus 170 mg gemcitabine every 3 weeks from the end of December 2023 to mid-July 2024, completing a total of 10 cycles. In mid-July 2024, the patient was initiated on the PD-1 inhibitor sintilimab at a dose of 100 mg every 3 weeks. Concurrently, the patient underwent radiotherapy targeting the lesion from mid-July to mid-August. From mid-August, the patient gradually developed bilateral ptosis, accompanied by generalized fatigue, a noticeable reduction in walking speed, impaired stair-climbing ability (limited to four flights with rest intervals) and decreased strength in both upper limbs. Over the following 2 weeks, the patient's symptoms progressively worsened, culminating in bulbar dysfunction characterized by dysarthria and dysphagia.

Chemotherapy was discontinued due to the patient's worsening clinical status 3 weeks after disease onset (Fig. 1A and B; Table I). The patient was admitted to the Department of Neurology. Physical examination revealed bilateral ptosis and proximal lower limb weakness (grade IV on the Medical Research Council scale) (9). Tendon reflexes were absent in the upper limbs and diminished in the lower limbs. The pharyngeal reflex was also absent. Electromyography and nerve conduction studies demonstrated widespread denervation without a decremental response on low-frequency repetitive nerve stimulation. The neostigmine test yielded negative results. Laboratory testing revealed elevated levels of creatine kinase at 1,633 U/l (normal range, 26-140 U/l), creatine phosphokinase-isoenzyme-MB at 100 U/l (normal range, 0-23 U/l) and cardiac troponin T at 0.782 ng/ml (normal range, 0-0.014 ng/ml). Serum anti-double-stranded DNA antibody was 186.6 IU/ml (normal range, 0-100 IU/ml) and anti-nucleosome antibody was 20.5 RU/ml (normal range, 0-20 RU/ml). Electrocardiography showed frequent premature ventricular contractions, while echocardiography findings were unremarkable. Brain MRI revealed no abnormalities (data not shown). Lumbar puncture demonstrated normal cerebrospinal fluid pressure and routine biochemical test results showed negative microbiological findings, and no malignant cells were identified (data not shown).

Figure 1 Longitudinal profiles of disease progression and therapeutic interventions. (A) Clinical timeline showing disease diagnosis and treatment milestones. (B) Clinical manifestation scores: ADL (left Y-axis); INCAT (right Y-axis). (C) Serum cytokine dynamics: TNF-α, IL-1β, IL-6 and IL-10 (left Y-axis); sIL-2R (right Y-axis). (D) Immunoglobulin kinetics: IgG, IgA and IgM (left Y-axis); IgE (right Y-axis). AG chemotherapy, chemotherapy with the cytarabine plus gemcitabine; EGF, efgartigimod; ADL, Activities of Daily Living; INCAT, Inflammatory Neuropathy Cause and Treatment; sIL-2R, soluble IL-2 receptor.

Table I Clinical manifestation scores at disease onset and during treatment.

Table I

Clinical manifestation scores at disease onset and during treatment.

Scoring system	Baseline	Week 2	Week 4	Week 5	Week 6	Week 7	Week 8 (EFG 1st)	Week 9 (EFG 2nd)	Week 10 (EFG 3rd)	Week 11 (EFG 4th)	Week 25
ADL	100	85	35	45	45	55	60	70	80	100	100
INCAT	0	1	7	6	6	5	4	2	1	0	0

[i] ADL, Activities of Daily Living; INCAT, Inflammatory Neuropathy Cause and Treatment.

Diagnosis and management

The patient was diagnosed with ICI-induced PRN and cardiomyopathy. Initial treatment with IVIG at a dosage of 0.4 g/kg, administered for 5 days, yielded no clinical improvement. The patient developed persistent chest tightness requiring supplemental oxygen. The muscle strength in the cervical region and extremities had markedly declined, rendering the patient bedbound. Progressive dysphagia and dysarthria necessitated a nasogastric tube for nutritional support.

Subsequently, corticosteroid therapy was initiated with intravenous methylprednisolone (240 mg daily for 5 days, followed by 120 mg daily for 3 days). This was subsequently transitioned to oral prednisone, starting at 60 mg per day and tapered by 5 mg per week to a maintenance dose of 30 mg. Although a slight improvement in limb weakness was observed, ptosis and swallowing difficulties persisted. In addition, the patient developed tongue muscle atrophy.

In October 2024, treatment with intravenous efgartigimod was initiated at a dose of 10 mg/kg once weekly, leading to a notable improvement in ptosis, swallowing and speech. Following the second dose, the patient's symptoms continued to improve, and the patient was able to resume oral intake, although slowly. The nasogastric tube was subsequently removed, and the patient was discharged. During weekly hospital visits for the third and fourth doses with concurrent clinical assessments, sustained symptomatic improvement was observed (Fig. 1A). No adverse events were observed during the course of treatment.

In December 2024, the patient returned for a follow-up visit. Physical examination revealed no neurological deficits. Blood testing showed that both muscle and cardiac enzyme levels were within normal ranges. As a result, chemotherapy with cytarabine plus gemcitabine was resumed. At the subsequent follow-up in February 2025, the patient remained clinically stable and had no complaints of discomfort.

The patient's functional status was evaluated using the Activities of Daily Living (ADL) scale (10) and the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (11). Rapid disease progression was noted within one month of symptom onset, with the ADL score declining to 35 points (range, 0-100 points) and the INCAT score rising to 7 points (range, 0-10 points) following IVIG therapy. Corticosteroid treatment led to modest improvement, with the ADL score increasing to 45 points and the INCAT score decreasing to 6. Notably, after initiation of efgartigimod treatment, the patient exhibited rapid improvement in both measures. Complete recovery of activities of daily functioning was achieved after the fourth dose of efgartigimod and the patient remained symptom-free without relapse during the three-month follow-up period (Fig. 1B; Table I). The patient continued cancer treatment with regular follow-ups every 2 months, and the condition was stable at the last follow-up.

Cytokine and immunoglobulin monitoring

Cytokine levels (TNF-α, IL-6, IL-10 and IL-2 receptor) were measured by flow cytometry as previously described (12). At disease onset, cytokine levels were significantly elevated. Although IVIG and corticosteroid therapy led to a reduction in cytokine levels, no corresponding clinical improvement was observed. Subsequent treatment with efgartigimod resulted in a further decline in cytokine levels (Fig. 1C; Table II). Following IVIG administration, serum IgG levels initially increased but later returned to normal. A gradual decrease in IgG was observed after the initiation of efgartigimod, while the levels of other immunoglobulins remained stable (Fig. 1D; Table II).

Table II Serum cytokine and immunoglobulin dynamics at disease onset and during treatment.

Table II

Serum cytokine and immunoglobulin dynamics at disease onset and during treatment.

Parameter	Baseline	Week 3	Week 5	Week 6	Week 8 (EFG 1st)	Week 9 (EFG 2nd)	Week 10 (EFG 3rd)	Week 11 (EFG 4th)	Week 17	Week 25	Normal range
Immunoglobulin
IgG, g/l	13.41	12.34	21.47	20.58	10.06	6.89	4.46	3.64	6.83	10.88	8.60-17.40
IgA, g/l	1.61	1.26	1.47	1.34	NA	0.91	0.9	0.94	1.25	1.49	1.00-4.20
IgM, g/l	0.74	0.5	0.66	0.71	NA	0.51	0.41	0.35	0.47	0.51	0.50-2.80
IgE, IU/ml	18	44	46	36	NA	34	27	30	20	20	0-200
Cytokines
TNF-α, pg/ml	8.9	21.4	NA	NA	11.9	12	8	6.6	4.4	4.1	0-8.1
IL-1β, pg/ml	5	5	NA	NA	5	5	<5.0	<5.0	<5.0	<5.0	0-5.0
IL-2R, IU/ml	485	1,389	NA	NA	531	635	503	501	260	287	223-710
IL-6, pg/ml	4.9	5.8	NA	NA	<2.0	3.1	<2.0	<2.0	4.9	5.2	0-3.4
IL-10, pg/ml	5	9.5	NA	NA	5	5	<5.0	<5.0	<5.0	<5.0	0-9.1

[i] IL-2R, IL-2 receptor.

Discussion

ICIs can cause severe, though rare, neuroimmune complications, such as myositis, myocarditis and PRN, typically emerging after one to two treatment cycles (3). The incidence of ICI-induced PRN is estimated to be between 0.1 and 0.3% (13), with clinical manifestations, including limb weakness and bulbar symptoms. Although corticosteroids and IVIG are considered first-line therapies, the associated mortality rate remains high, reaching up to 60% (4,5). In the present case, the patient exhibited a limited clinical response to corticosteroids and IVIG. However, substantial neurological and cardiac improvement was achieved following administration of efgartigimod, a novel immunosuppressive agent and first-in-class FcRn antagonist.

During the course of treatment, cytokine and immunoglobulin levels were monitored, noting initial elevations indicative of immune activation. Although cytokine levels decreased following conventional treatment, no corresponding clinical improvement was observed, suggesting that cytokine-driven pathways may not be dominant in the pathogenesis of irAEs in the patient.

Importantly, antibody-mediated immune processes have been increasingly implicated in the development of irAEs. Previous studies have reported that up to 40% of patients developed encephalitis, 34.4% had myasthenia gravis and 22% of patients experienced peripheral neuropathy and Guillain-Barré Syndrome and tested positive for autoantibodies (14,15). The most frequently detected neuro-antibodies include anti-acetylcholine receptor antibodies, anti-Ma family member 2 antibodies and anti-Hu antibodies (15). Additionally, a range of autoantibodies has been detected in ICI-induced myocarditis, including those targeting myosin heavy chain, cardiac troponin I and other cardiac antigens, such as β-1 adrenergic receptor, muscarinic M2 receptor and Na-K-ATPase (16). Nonetheless, a significant proportion of patients remain negative for these antibodies, suggesting the involvement of alternative pathogenic mechanisms or the presence of unidentified antibodies.

In the patient of the current study, the presence of positive serum anti-double-stranded DNA antibodies, along with significant clinical improvement and a sustained reduction in IgG levels following efgartigimod treatment, supports the hypothesis that antibody-mediated immune responses play a central role in the pathogenesis of ICI-induced paraneoplastic neurological syndrome. Efgartigimod, originally developed for the treatment of myasthenia gravis and other autoimmune disorders, functions by binding to FcRn, thereby preventing the recycling of IgG and promoting its degradation (7). This mechanism reduces circulating IgG levels without inhibiting IgG synthesis, offering a promising therapeutic option for patients who are unresponsive to conventional immunosuppressive therapies. Within the therapeutic context of irAEs, efgartigimod shows potential efficacy through the targeted clearance of pathogenic autoantibodies, which in turn attenuates downstream inflammatory cascades. Furthermore, a previously reported case demonstrated the significant efficacy of efgartigimod in treating ICI-induced myositis, myocarditis and myasthenia gravis (8), further emphasizing the therapeutic potential of FcRn antagonists in eliminating pathogenic autoantibodies and supporting FcRn blockade as a promising strategy for managing severe neurological and cardiac irAEs.

While the present case demonstrates promising results, the generalizability of these findings is inherently limited by the single-patient design. Multicenter collaborations and larger cohorts of patients with refractory irAE are needed to validate the efficacy of efgartigimod. Although the patient exhibited positive serum anti-double-stranded DNA antibodies, anti-nucleosome antibodies and initially elevated immunoglobulin levels, further investigation is necessary to elucidate the role of these antibodies in the onset and progression of ICI-induced PRN. Comprehensive serological profiling, including testing for anti-ganglioside, onconeural, myositis-specific and myasthenia gravis-associated antibodies, along with advanced molecular analyses, will be essential for uncovering the underlying mechanisms of irAE pathogenesis (3).

In light of the findings of this case study, several clinical applications for efgartigimod may also be proposed. This agent may offer a particular benefit to patients with ICI-induced neuroimmune complications who are unresponsive to conventional treatments such as corticosteroids and IVIG. Therapeutic monitoring should include regular assessments of serum IgG levels and other immune markers to enable individualized treatment adjustments. Future research should focus on refining patient selection criteria and establishing standardized protocols for the clinical use of FcRn antagonists in the management of ICI-induced irAEs.

While this case provides compelling evidence supporting the efficacy of efgartigimod in treating ICI-induced PRN and cardiomyopathy, further research is required to establish its role in broader clinical practice. The limitations of this report, including the single-patient design and the short duration of follow-up, should be acknowledged. Future studies should aim to address these gaps to inform evidence-based clinical decision-making.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

Authors' contributions

SD was involved in the conceptualization of the study, data curation, formal analysis, writing the original draft, and reviewing and editing the manuscript. ZW performed data curation and writing of the original draft. QW contributed with data curation, visualization, and reviewing and editing the manuscript. ZH was involved in visualization, and reviewing and editing the manuscript. JD and SW contributed by reviewing and editing the manuscript, and aided study conceptualization. All authors have read and approved the final version of the manuscript. Two authors have checked and confirmed the authenticity of the raw data.

Ethics approval and consent to participate

The study involving human participants was approved by the Ethics Committee of Zhongshan Hospital, Fudan University (approval no. CR2025-001). All procedures were conducted in accordance with the principles of the Declaration of Helsinki.

Patient consent for publication

Written informed consent was obtained from the patient for the publication of this case report, including the publication of potentially identifiable data.

Competing interests

The authors declare that they have no competing interests.

References