Therapeutic Combinations of Immune-Modulating Antibodies in Melanoma and Beyond

Immune-modulating antibodies demonstrate activity in increasing numbers of malignancies, and more will be developed in the coming decade. Although active as single agents, optimal outcomes will require combination therapies for many patients. Currently, most combinations are based on either PD-1/PD-L1 antagonists or anti-CTLA-4. The combination of anti-PD-1 with anti-CTLA-4 demonstrates promising activity in metastatic melanoma and metastatic renal cell carcinoma and will be tested in multipe other malignancies. Future combinations will likely involve two or more checkpoint inhibitors, a checkpoint inhibitor in combination with an agonist of costimulation, combinations of costimulatory agents or combinations with antibodies that alter lymphyocyte trafficking. Although opportunities for effective combinations are available, major challeneges include the potential for autoimmune toxicity and the selection of patients.