Role of CTLA-4 blockade and dacarbazine therapy following anti-PD-1 resistance in melanoma

Many patients with advanced melanoma eventually stop responding to PD-1 immunotherapy, and effective treatments are limited. Recent studies suggest that older chemotherapy drugs such as dacarbazine and temozolomide may work better after prior PD-1 therapy and can stimulate the immune system when combined with CTLA-4 blockade (ipilimumab). This review summarises clinical evidence and biological mechanisms supporting these combinations, including how chemotherapy-induced DNA damage can release tumour antigens, activate interferon pathways, and reawaken exhausted T cells. Because these regimens are relatively safe, inexpensive, and widely available, they may provide a realistic treatment option for patients in health systems where modern cell-based therapies are not accessible. Further clinical trials with integrated biomarker research are needed to identify which patients benefit most from this approach.