Management of MOG antibody-associated disease by pembrolizumab and radiation myelopathy in an elderly patient: A case report and literature review

ABSTRACT

Immunotherapy and radiotherapy are important means for treating solid tumors. Both treatment methods can potentially cause neurologic injuries. Timely identification, diagnosis, and early treatment play a crucial role in the recovery from neurologic damage. This case report describes a 69-year-old woman with esophageal and oropharyngeal cancer who developed neurological complications after radiotherapy and immunotherapy. She experienced radiation-related motor impairment and symptoms returned after treatment with bevacizumab and corticosteroids. Later, she developed a rare demyelinating neuropathy, diagnosed as MOG antibody-associated disease (MOGAD), likely triggered by immune checkpoint inhibitors, which is a very rare adverse drug reaction. Her condition improved with cessation of immunotherapy and the administration of steroid pulse therapy. Despite treatment interruptions due to side effects, her survival period was favorable, suggesting that reduced-dose therapy in elderly patients may not diminish its antitumor effect. This case emphasizes the need for vigilance in recognizing rare complications and rational antitumor treatment intensity in geriatric oncology.

Background

According to the World Health Organization’s definition, individuals who are 65 years of age and older are classified as elderly. Among the newly diagnosed cases of cancer, elderly patients make up 53% of the total, highlighting their significant presence in the disease demographic.¹ Elderly patients are often with poor physical condition and multiple comorbidities and the anti-cancer treatment in elderly patients is characterized by its uniqueness and complexity.² Thus, the safety of anticancer treatment in elderly patients deserves more attention.

Immune checkpoint inhibitors (ICIs), such as PD-1 antibodies, can cause neurological immune-related adverse events (NAEs), categorized into central (CNS) and peripheral (PNS) nervous system reactions, with incidence rates of 5.5% and 0.5%, respectively.^3,4 MOGAD is an immune-mediated demyelinating disorder of the central nervous system that has rarely been linked to PD-1 inhibitor therapy. Here, we present a case of an elderly patient with MOGAD after immunotherapy and limb motor dysfunction after radiotherapy, offering insights for safe cancer treatment in the elderly.

Patient presentation

In November 2023, a 69-year-old female with localized oropharyngeal cancer was admitted to the Oncology Department of Shanghai Geriatric Medical Center. She presented with recent symptoms of bilateral lower limb weakness and numbness, which began in the left leg before involving the right. The July and September 2023 cervical spine MRIs both revealed high signal intensity lesions (Figure 1). A subsequent PET-CT scan showed no new metastatic lesions, and comprehensive evaluation found no significant evidence of disease progression.

Figure 1.

Radiological assessment results for nerve damage due to radiation therapy.

The July and September 2023 MRIs revealed evident spinal cord lesions within the radiation field. After treatment with steroids, bevacizumab, a follow-up MRI in February 2024 demonstrated significant improvement in the lesions compared to the prior findings.

The patient’s medical history revealed a diagnosis of cervical esophageal cancer in September 2022. She underwent concurrent chemoradiotherapy until November 2022, receiving radiotherapy (60 Gy in 30 fractions) with weekly chemotherapy (73 mg paclitaxel + 173 mg carboplatin). This was followed by adjuvant chemotherapy (197 mg paclitaxel + 110 mg nedaplatin q3w), completed in March 2023. Four months later, she was diagnosed with oropharyngeal cancer. From July to October 2023, she received four cycles of the PD-1 inhibitor pembrolizumab (200 mg) combined with the PF chemotherapy regimen (3.0 g 5-fluorouracil on day 1 and 40 mg cisplatin on days 1–2, q3w).

Retrospective comparison of imaging studies identified a preexisting hyperintense lesion in the neck prior to immunotherapy. This was suspected to be radiotherapy-related damage, as it appeared within the radiation field which had received a high total dose of 60 Gy. Consequently, the patient received dexamethasone (5 mg daily for 5 days) combined with bevacizumab (200 mg, q2w) to reduce vascular permeability, along with supportive treatments including vitamin C, vitamin B1, and mecobalamin from November 7 to December 30, 2023. Following this, her lower limb muscle strength returned to normal.

After this neurological improvement, the patient resumed pembrolizumab on January 8, 2024. However, lower limb weakness recurred one week later. A follow-up MRI on February 28 showed a partial response in the oropharyngeal tumor, ruling out disease progression or other new lesions (Figure 2). Infection markers, including C-reactive protein, white blood cell count, neutrophil count, and procalcitonin, were within normal ranges, effectively excluding infectious causes. Although a lumbar puncture and electromyography were recommended, the patient refused. Instead, a fixed cell-based assay (CBA) was performed on the patient’s serum for demyelinating diseases, which was positive for MOG antibody (titer 1:32). Tests for paraneoplastic syndromes were negative (Supplementary data Tables 1 and 2; Figure 3).

Figure 2.

Changes in tumor lesions before and after treatment.

The images demonstrate serial changes in the primary oropharyngeal cancer (OPC) lesion. The July 2023 scan depicted the baseline tumor status. Following combined chemotherapy and immunotherapy, the patient achieved partial response (PR), as evidenced by the February 2024 imaging. The patient developed progressive disease (PD) in May 2024.

Figure 3.

Demyelination-related antibody staining.

Green staining in the image corresponds to control cell (HEK293T cells). The middle panel displays target antibody staining (red: positive signal). The right panel presents merged staining (green: control; red: target). Only MOG antibody exhibits a positive signal in serum staining. This image was obtained using a cell-based indirect immunofluorescence assay at a magnification of 200×.

From March 11 to 15, 2024, the patient received intravenous immunoglobulin (15 g) and methylprednisolone pulse therapy (120 mg). Upon discharge, she was prescribed a tapering regimen of oral prednisone. Her limb muscle strength improved from grade II-III to IV-V (Figure 4). The best treatment response achieved during her course was a partial response, with a progression-free survival of 10 months and an overall survival of 12 months (Supplementary data Table 3; Figure 5).

Figure 4.

Steroid, IVIG dosage and corresponding muscle strength changes.

The figure illustrates changes in the patient’s muscle strength during steroid and immunoglobulin therapy, with associated drug doses annotated.

Figure 5.

The timeline of the patient’s treatment.

Blue and green squares represent the patient’s anti-tumor treatment regimen, while dots indicate interventions administered after the patient developed adverse reactions to the therapy. The patient was diagnosed with oropharyngeal cancer and achieved 10 months of progression-free survival and 12 months of overall survival following the completion of treatment (EC: Esophageal Cancer; OPC: Oropharyngeal Cancer; PD: Progressive Disease; MP: Methylprednisolone; Pred: Prednisone; IVIG: Intravenous Immunoglobulin).

Discussion

Immune checkpoint inhibitors can trigger demyelination through T-cell mediated autoimmunity, molecular mimicry between tumor and neural antigens, and blood-brain barrier disruption enabling neuroinflammation.⁵ Here we report a case of MOGAD in an elderly female with oropharyngeal cancer following pembrolizumab treatment – a rare demyelinating adverse event affecting the central nervous system. Although the possibility of radiation-related injury or coincidental events cannot be entirely excluded – particularly given the patient’s history of radiotherapy – the close temporal relationship between the initiation of immunotherapy and the onset of neurological symptoms suggests a potential causal link. This is further supported by the fact that MOGAD is not typically considered a paraneoplastic syndrome.⁶ The diagnosis was established based on serological testing and clinical evaluation,⁷ although the absence of characteristic imaging findings introduces some diagnostic uncertainty. Notably, the patient demonstrated significant neurological improvement following immunomodulatory therapy. In contrast to a previously reported case involving a young melanoma patient who developed neurological symptoms after six months of treatment, the present case occurred in an elderly patient with delayed neurological manifestations.⁸

A notable aspect of this case is that the patient had previously developed radiation-related spinal cord injury following radiotherapy for esophageal cancer, and now presented with MOGAD during immunotherapy, suggesting that elderly cancer patients may accumulate multiple treatment-related toxicities after multimodal therapy. Nevertheless, even after immunotherapy was temporarily discontinued due to MOGAD, the patient achieved a survival of 12 months, which is consistent with the average survival of 13 months reported for oropharyngeal cancer,⁹ indicating no significant compromise in treatment efficacy.

This case raises an important clinical question: should elderly patients necessarily receive standard-intensity antitumor therapy? Available evidence indicates that the incidence of immune-related toxicity in older adults is not significantly higher than in younger patients^10,11 and they derive similar therapeutic benefits.^11,12 The favorable outcome in this patient despite treatment interruption provides a rationale for exploring dose de-escalation or intensity-adjusted regimens in the geriatric population.

We recommend the following in the management of elderly cancer patients: first, enhancing recognition of rare neurological toxicities such as MOGAD; second, implementing comprehensive geriatric assessment before treatment using screening tools such as G8 and VES-13 to identify vulnerable individuals^13,14; and finally, establishing dynamic monitoring systems to balance efficacy and toxicity in an individualized manner. Through precise toxicity management and intensity modulation, more elderly patients may safely benefit from immunotherapy.

Elderly patients receiving ICIs may develop MOGAD as a potential complication. Oncologists should be aware of such rare but serious adverse events in elderly patients with anti-tumor therapy and consider vulnerability evaluation as a necessary means to decrease the therapy risks in elderly patients.

Biographies

Pengfei Zhang is a Deputy Chief Physician in the Department of Medical Oncology at Shanghai Geriatric Medical Center. His academic appointments include roles in the Precision Medicine Expert Committee of the Cancer Rehabilitation Branch, Chinese Society of Gerontology and Geriatrics, and the Oncology Clinical Translational Research Public Welfare Fund Management Committee, China Primary Health Care Foundation. He has led a General Project from the National Natural Science Foundation of China and multiple provincial- and ministerial-level projects. As first or corresponding author, he has published over 30 SCI papers in journals such as Journal of Hepatology, Innovation, Molecular Cancer, Journal of Hematology & Oncology, Cell Death & Disease, and Oncogene.

Xu Zhou serves as a Deputy Chief Physician in the Department of Otorhinolaryngology at Zhongshan Hospital, Fudan University. His academic roles include positions in the Voice Disorders Group of the Shanghai Medical Association, the Sleep Medicine Committee of the China Medicine Education Association, and several other professional societies such as the Chinese Microcirculation Society. He also acts as a quality control inspector for the Shanghai Clinical Quality Control Center for Otorhinolaryngology Head and Neck Surgery and as a peer reviewer for the Shanghai Science and Technology Commission Natural Fund and Shanghai Sailing Program. Dr. Zhou has published over ten papers as first or corresponding author in core international journals, including SCI-indexed publications, and has secured research grants from the Shanghai Municipal Health Commission and the Fudan University Youth Research Fund.

Qian Li is a Deputy Chief Physician in the Department of Medical Oncology at Zhongshan Hospital, Fudan University, and Deputy Director of the Department of Medical Oncology at Zhongshan Hospital (Meilong Branch). She holds a Ph.D. in Oncology and serves as Secretary of the Shanghai Chemotherapy Quality Control Center for Oncology. She is a Standing Committee Member of the CACA Integrated Rehabilitation Committee for Gastric Cancer and a Committee Member of the Breast Cancer Specialty Committee of the Shanghai Women Doctors’ Association. She also serves on the Youth Committees of the Tumor Internal Medicine Committee of the Shanghai Medical Association and the Palliative Care Committee of the Chinese Medical Association. In addition, she is a Member of the Precision Medicine Expert Committee of the Cancer Rehabilitation Branch of the Chinese Society of Gerontology and Geriatrics and the CACA Integrated Rehabilitation Committee for Bone and Soft Tissue Tumors. Dr. Li is GCP certified and has served as Sub-Investigator and Quality Assurance lead in over 30 international and domestic multicenter clinical trials for novel drugs. She has participated in and presided over multiple provincial and municipal research projects and has published numerous papers in SCI-indexed journals.

Funding Statement

The present study was supported by grants from Shanghai Sailing Program [grant no. 23YF1438600] and Zhongshan Hospital Special Fund for Specialist Physicians [grant no. ZP2022-001] to Xiao Wang.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

The current study adheres to internationally accepted ethical standards. Written informed consent for publication was obtained from the patient’s legal guardian.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2025.2588020.