Salvage nivolumab plus temozolomide associated with improved survival and clinical benefit in refractory melanoma: a retrospective cohort study

Introduction Patients with metastatic melanoma who progress on standard of care therapy have limited treatment options. This study evaluates the efficacy of nivolumab combined with temozolomide compared to temozolomide alone in this refractory setting. Methods We conducted a retrospective cohort study of 44 patients with metastatic melanoma who progressed on prior immunotherapy and systemic therapies. Patients were chemotherapy-naïve and treated at a single center between 2020-2025. Endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and progression-free survival (PFS). Results Patients treated with nivolumab/temozolomide had improved CBR by over fourfold compared with temozolomide alone. (OR 4.276, 95% CI:1.198-15.268; p=0.025). Median OS was 11.8 months (95% CI: 6.02, NA) with nivolumab/temozolomide versus 5.49 months (95% CI: 1.91-8.97) with monotherapy. Combination therapy was also associated with a lower hazard of death (HR 0.44; 95% CI: 0.205-0.923; p=0.030) and trended toward a lower hazard of progression (HR; 0.531 CI: 0.280-1.008; p=0.053). Exploratory analysis showed a significant treatment-LDH interaction was identified for OS (p=0. 043). Within the subgroup of patients with a baseline LDH over 2 times the upper limit of normal, combination therapy was associated with a significantly reduced hazard of death (HR: 0.183; 95% CI: 0.049-0.690; p=0.012) and progression (HR: 0.205; 95% CI: 0.060-0.692; p=0.011). Nivolumab/temozolomide had numerically higher ORR (36% vs. 10.5%, p=0.053). Combination therapy demonstrated a significantly higher CBR among patients with BRAF mutations compared to monotherapy (90.0% vs. 20.0%, p=0.017). Conclusions Nivolumab and temozolomide combination therapy may represent a viable salvage regimen for refractory melanoma.