Nivolumab plus temozolomide (Nivo/Tem) vs. temozolomide monotherapy in refractory melanoma.

Abstract

e21507 Background: While immunotherapy (IT) is first-line therapy for advanced melanoma, many patients are refractory, necessitating alternative treatments. Patients with refractory melanoma have limited treatment options, particularly when they have poor performance status. This study evaluated the clinical outcomes and safety of combining Nivo/Tem compared to Tem monotherapy in refractory melanoma. Methods: We conducted a single-center retrospective cohort study of 44 patients with metastatic melanoma. Eligible patients had documented disease progression on prior anti-PD-1+/- ipilimumab or relatlimab and other available systemic treatments. Patients with prior chemotherapy or uveal melanoma were excluded. Patients treated with Nivo/Tem (n=25) were compared to a control group receiving Tem alone (n=19). Endpoints included objective response rate (ORR), Clinical Benefit Rate (CBR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using the Kaplan-Meier method. Cox proportional hazards models estimated hazard ratios (HR) and 95% CI, including exploratory interaction testing by baseline LDH. Results: Baseline characteristics were comparable, (p>0.05), including median lines of therapy (2 vs. 2), M1c/d stage (84% vs. 79%), and elevated LDH (75% vs. 74%). ORR (32% vs 10.5%; p=0.108) and CBR (48% vs 31.6%; p=0.421) were numerically higher in the combination arm but did not reach statistical significance. Median OS was 359 days for Nivo/Tem vs. 167 days for Tem (HR 0.44; 95% CI:0.20-0.93; p=0.032). Median PFS was 111 days for Nivo/Tem vs. 59 days for Tem (HR 0.53; 95% CI: 0.28-1.01; p=0.055), which approached but did not reach statistical significance. Multivariate analysis identified a significant treatment-LDH interaction for both OS (p=0.024) and PFS (p=0.018). Outcomes were similar in the normal LDH group, whereas the higher risk of death and progression was significantly attenuated in the combination group; the HR for combination therapy was 0.34 (p=0.01) for OS and 0.45 (p=0.02) for PFS. Conclusions: Nivo/Tem improved OS compared to Tem alone in immunotherapy-refractory melanoma, with both OS and PFS benefits particularly pronounced in patients with elevated LDH. Improvement in ORR did not reach statistical significance but appeared to have clinical significance. These findings suggest that chemo-immunotherapy may be a viable salvage strategy for patients with aggressive, refractory disease, particularly when other options are not viable.