Real-world outcomes of low-dose nivolumab in advanced malignancies

Dear Editor, Immune checkpoint inhibition with PD-1/PD-L1 blocking monoclonal antibodies has significantly improved survival outcomes in various malignancies.[1] However, access to these therapies remains limited in many low- and middle-income countries due to high costs, contributing substantially to financial toxicity.[2] Emerging evidence suggests that low-dose immunotherapy may offer clinical benefits, making it a promising area of interest, especially in resource-constrained settings.[3-5] In our current study, we aimed to evaluate the therapeutic efficacy of low-dose nivolumab, an anti-PD-1 monoclonal antibody. We conducted a single-center, real-world, retrospective analysis of patients with advanced cancers that lacked standard treatment options and for which standard-dose nivolumab is an approved therapy. These patients received a flat low dose of nivolumab (20-40 mg every 3 weeks).[4,5] Data, including patient demographics, cancer history, immunotherapy regimen (dose, modifications, compliance), and adverse events, were collected from electronic medical records. All patients provided informed consent, and the study was approved by the institutional review board of BALCO Medical Centre (approval number: BMCIRB/2025/19). Between March 2022 and October 2024, 100 patients received low-dose nivolumab. The median age was 54 years (26-86), with 17% being female. All patients had stage IV disease, and 85% had an ECOG performance status of 0 or 1. The most common diagnosis was head and neck squamous cell carcinoma (HNSCC) (66%), followed by gastric cancer (8%) and renal cell carcinoma (7%). Other cancer types included lung (4%), esophageal (3%), melanoma (3%), cervical (2%), urothelial (2%), colorectal (1%), anal canal (1%), and carcinoma of unknown primary (1%). Nivolumab was combined with chemotherapy in 83% of patients. The median number of prior lines of therapy was 2 (1-4), and the median number of nivolumab cycles administered was 4 (1-29). Nivolumab was administered at 20 mg every 3 weeks in 78% of patients and 40 mg every 3 weeks in 22% of patients. PD-L1 combined positive score (CPS) status was available for 44 patients (>50 in 13, 10-50 in 20, <10 in 11), and one patient had microsatellite instability-high (MSI-high) status. The best overall responses observed were complete response (CR) in 4%, partial response (PR) in 18%, stable disease (SD) in 30%, and progressive disease (PD) in 48% of patients. At a median follow-up of 17 months, 66 patients had died. The median progression-free survival (PFS) was 5.8 months (95% CI: 3.2-13.8), with HNSCC patients demonstrating a median PFS of 5.0 months (95% CI: 2.7-7.3). The median overall survival (OS) was 9.0 months (95% CI: 4.2-13.8), with HNSCC patients demonstrating a median OS of 8.4 months (95% CI: 5.8-10.2). Notably, 13 patients (5 with HNSCC, 2 with melanoma, 2 with esophageal cancer, and 1 each with lung, stomach, anal canal, and urothelial cancers) had a PFS of more than 12 months, suggesting a significant benefit in this heavily pretreated patient population. Two metastatic melanoma patients exhibited durable responses of 22 and 35 months. Dosing of nivolumab did not significantly affect OS (20 mg: 8.86 months vs 40 mg: 9.58 months, P = 0.76). Low-dose nivolumab was well tolerated, with hypothyroidism (8%) being the most common toxicity. We acknowledge that concurrent chemotherapy in 83% of patients may have influenced the outcomes, which is a limitation of our study. In conclusion, our findings suggest that low-dose nivolumab could be a cost-effective treatment option for patients with advanced malignancies in settings where standard-dose immunotherapy is unaffordable due to prohibitive costs. While these results are promising, further prospective studies are necessary to validate the noninferiority of low-dose nivolumab and to identify the patient subgroups most likely to benefit from this approach. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.