Remarkable response to personalized combination immunotherapy of nivolumab plus ipilimumab in an 84-year-old patient with locally advanced squamous cell carcinoma: a case report

Introduction

Nivolumab plus ipilimumab (NIVO + IPI) combination therapy is effective in advanced non-small-cell lung cancer (NSCLC) patients. However, the rates of grade 3 or 4 treatment-related adverse events (44% vs. 34%) and treatment discontinuation (29% vs. 21%) remain higher in patients aged ≥75 years than in younger patients (1), which necessitate exploration of dose optimization strategies in this demographic. We present an 84-year-old, locally advanced NSCLC patient who received a tailored-dose strategy of NIVO + IPI to mitigate the risk of severe treatment-related adverse events. We present this article in accordance with the CARE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0194/rc).

Case presentation

An 84-year-old Asian man, a former smoker with a 25-pack-year history and chronic obstructive pulmonary disease (COPD), presented with a 3-month history of cough and low-grade fever. His baseline body mass index (BMI) was 17 kg/m², Eastern Cooperative Oncology Group performance status (ECOG PS) was ≥2, serum creatinine was 116 µmol/L, and serum albumin was approximately 33 g/L. Computed tomography (CT) revealed a 140 mm soft tissue mass causing obstructive pneumonia in the right mid-upper lobe (Figure 1). The superior vena cava (SVC), right upper pulmonary vessels, and chest wall were invaded, accompanying hilar and mediastinal lymph node metastasis (Figure 2). Immunohistochemical analysis revealed positivity for cytokeratin (CK) and p40, with a Ki-67 index of 80% and a programmed death-ligand 1 (PD-L1) expression level of 33%. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed following supportive treatment for pneumonia, confirming the diagnosis of non-keratinizing squamous cell carcinoma (Figures 3,4). Staging confirmed as IIIC (cT4N2M0) disease. Comprehensive genomic profiling revealed no actionable driver mutations.

Figure 1 Timeline of personalized combination immunotherapy and follow-up imaging. (A) Baseline chest CT showing a 140 mm soft tissue mass in the right mid-upper lobe with associated obstructive pneumonia. (B) Restaging chest CT after two cycles of combination immunotherapy demonstrating SD, with early regression of the primary lesion, metastatic lymph nodes, and chest wall invasion, alongside resolution of the SVC involvement. (C) Follow-up chest CT after four cycles showing a partial response, with the primary mass regressed to 50 mm × 11 mm with mild heterogeneous enhancement. CT, computed tomography; EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle aspiration; irAE, immune-related adverse event; MDT, multidisciplinary team; PFS, progression-free survival; PR, partial response; SD, stable disease; SVC, superior vena cava.

Figure 2 Chest computed tomography scans showing the primary tumor and superior vena cava invasion (A) before and (B) after four cycles of combination immunotherapy.

Figure 3 Diagnostic bronchoscopic and histopathological findings. (A) Bronchoscopy revealed extrinsic compression and occlusion of the right middle lobe medial segmental bronchus. (B) Pathological assessment confirmed non-keratinizing squamous cell carcinoma (hematoxylin and eosin stain, ×200).

Figure 4 Immunohistochemical characterization of the tumor immune microenvironment (hematoxylin counterstain). (A) Low-magnification overview (40×) illustrating the broad and diffuse distribution of CD8⁺ T cells throughout the pretreatment biopsy specimen. (B) High-magnification representative image (200×) demonstrating dense infiltration of CD8⁺ T cells within the tumor nests.

Nevertheless, based on advanced age, poor performance status, concerns about potential toxicities, and the Geriatric 8 (G8) screening score of 7, the multidisciplinary team recommended a personalized-dose strategy. This recommendation aligned with the patient’s and his family’s strong preference to minimize adverse effects. Following detailed consultation and informed consent, NIVO 200 mg (4 mg/kg) every 3 weeks (Q3W) plus IPI 50 mg (1 mg/kg) every 6 weeks was administered.

Restaging CT after two cycles demonstrated stable disease via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, with early regression of the primary lesion, metastatic lymph nodes, and chest wall invasion along with resolution of the SVC nodule (Figure 1B). During this period, the patient developed a mild rash, which was managed with oral ebastine and resolved without dose interruption. After four cycles of treatment, a follow-up CT confirmed a partial response (PR). The primary mass had significantly regressed to 50 mm × 11 mm with only mild heterogeneous enhancement (Figures 1C,2B). No grade ≥2 immune-related adverse events (irAEs) occurred, and prophylactic antiemetics were administered during cycles 3 and 4 to prevent nausea. The NIVO + IPI combination therapy was planned to continue for a year. During the 10-month follow-up, the patient reported symptomatic improvement and exhibited sustained disease control with no disease progression or treatment discontinuation reported till the time of this submission.

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report and accompanying images was waived from patient consent according to the ethics committee of The First Affiliated Hospital of Guangzhou Medical University.

Patient perspective

During the treatment course, the medical team explained the options to me and my family in detail, including the benefits and risks of the reduced-dose regimen. Given my age and overall condition, we jointly agreed with this strategy. Throughout the treatment period, my main discomforts were a skin rash and nausea, but both resolved quickly and did not affect my daily life. Compared with chemotherapy, I did not experience any fatigue, loss of appetite, or other side effects. After completing four cycles of treatment, the tumor had shrunk significantly, which gave me great confidence. At the 10-month follow-up, my symptoms of fever and cough were much better, and the tumor had not progressed. I was able to carry out my daily activities, take walks, and spend time with my family. I was highly satisfied with the medical team’s close observation and their individualized approach to my care.

Discussion

Immunotherapy has transformed the management of advanced NSCLC, with the combination of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors offering particular promise. Existing evidence, such as CheckMate 817, demonstrates the feasibility of immunotherapy in special populations, yet it provides no specific guidance for vulnerable, low-BMI elderly patients (G8 ≤14), in whom standard flat-dose regimens may lead to excessive systemic exposure (1,2). Although some octogenarians achieve durable responses to NIVO + IPI, the high rate of irAEs and treatment discontinuation remains a concern (3). Given the poor tolerability of chemotherapy in frail elderly patients and the potential long-term efficacy advantage of NIVO + IPI over pembrolizumab monotherapy in patients with low PD-L1 expression, we selected this combination for our personalized-dose strategy. By integrating pharmacokinetic (PK) simulations with geriatric assessments, we then proposed a weight-normalized regimen tailored to vulnerable, low-BMI octogenarians (4,5).

The absence of standardized guidance for patients over 80 has led to marked heterogeneity in NIVO + IPI prescribing patterns. Given that elderly Asian patients with advanced NSCLC frequently present with low body weight, standard flat-dose regimens (360 mg Q3W), typically optimized for an 80 kg reference population, result in disproportionately high exposure in lighter patients (6,7). Our PK simulation directly supported that for our 50 kg patient, the 200 mg dose (4 mg/kg) provides a weight-normalized exposure equivalent to that of the standard flat dose in heavier individuals (Figure 5) (8). Based on the maximum effect (Emax) model and phase I data, NIVO 3 mg/kg achieves sustained PD-1 receptor occupancy >70% for >2 months, and the predicted receptor occupancy curves for the 200 mg (50 kg) and 360 mg (80 kg) regimens were nearly overlapping, with comparable concentration profiles (Figure 5) (9). Consistent with these findings, a phase III randomized study on head and neck cancer and studies in NSCLC using low-dose NIVO demonstrated both safety and efficacy of low-dose regimens (10,11).

Figure 5 Simulated PK and PD profiles of NIVO. Comparative simulations are shown for (A) the standard flat-dose regimen (360 mg in an 80 kg reference individual) and (B) the weight-optimized regimen (200 mg in the 50 kg patient). Predicted serum NIVO concentrations (yellow lines, left Y-axis) indicate comparable exposure between regimens, with an estimated Cmax of approximately 60 μg/mL in both cohorts. Corresponding PD-1 receptor occupancy on circulating T cells (blue lines, right Y-axis) remains near-maximal (>99%). Cmax, maximum serum concentration; NIVO, nivolumab; PD, pharmacodynamic; PD-1, programmed cell death protein 1; PK, pharmacokinetic.

Despite the comparable efficacy across age groups in some immunotherapy studies, the relationship between advanced age and progression-free survival was not linear, indicating distinct heterogeneity in elderly patients with advanced NSCLC (12). The potential explanation for the favorable outcome is that COPD may have fostered a “hot” immune tumor microenvironment characterized by increased CD8⁺ T-cell infiltration and enhanced tumor immunogenicity, leading to increased responsiveness to immunotherapy. The immunohistochemical analysis of the patient’s pretreatment biopsy specimen revealed abundant CD8⁺ cytotoxic T lymphocytes diffusely infiltrating the tumor parenchyma, providing histopathological evidence of an inflamed tumor microenvironment in this COPD patient (Figure 4). Although COPD is associated with a poorer prognosis in lung cancer, it may paradoxically serve as a strong protective factor during immunotherapy (13). This may explain the significant response of reduced-dose NIVO + IPI for this patient, and why a subset of octogenarian patients with notable survival benefits despite their compromised baseline condition.

We describe an exploratory, personalized-dose strategy of NIVO + IPI in a frail 84-year-old, stage IIIC NSCLC patient. Guided by preliminary clinical evidence and PK models, this case suggests that in selected elderly patients, dose-optimized combination immunotherapy may achieve a durable response without compromising safety. While the observed response and manageable safety profile in this case illustrate the potential feasibility of dose de-escalation, the inherent limitations of a single case and the restricted follow-up period preclude definitive conclusions on the long-term efficacy of this approach.

Conclusions

In summary, this case demonstrates that a personalized-dose combination immunotherapy regimen can achieve a remarkable, durable response with a favorable safety profile in a fragile octogenarian patient. Incorporating comprehensive geriatric evaluation and pharmacokinetic rationales allows for successful dose optimization, balancing efficacy and toxicity in this vulnerable population and warranting further investigation in prospective clinical studies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0194/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0194/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0194/coif). S.L. serves as an unpaid editorial board member of Translational Lung Cancer Research from February 2025 to January 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report and accompanying images was waived from patient consent according to the ethics committee of The First Affiliated Hospital of Guangzhou Medical University.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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