Significant enthusiasm currently exists for new immunotherapeutic strategies: 
blocking the interaction between programmed death-1 receptor on T-cells and 
programmed death-ligand 1 on tumor cells to boost immune system stimulation to 
fight cancer. Immunomodulation with the antiprogrammed death-1/programmed 
death-ligand 1 monoclonal antibodies has shown to mediate tumor shrinkage and 
extend overall survival from several pivotal phase I/II studies in melanoma, 
renal cell carcinoma, and non-small cell lung cancer. This has prompted multiple 
large ongoing phase III trials with the expectation for fast-track FDA approvals 
to satisfy unmet medical needs. Compounds targeting the programmed death-1 
pathway that are in clinical trials fall into two major categories, namely 
antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and 
antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and 
MSB0010718C. We reviewed the clinical efficacy and safety of each compound based 
upon major registered clinical trials and published clinical data. Overall, 
response rate of more than 20% is consistently seen across all these trials, 
with maximal response of approximately 50% achieved by certain single 
antiprogrammed death-1 agents or when used in combination with cytotoxic 
T-lymphocyte antigen-4 blockade. The responses seen are early, durable, and have 
continued after treatment discontinuation. Immune-related adverse events are the 
most common side effects seen in these clinical trials. Overall, the skin and 
gastrointestinal tract are the most common organ systems affected by these 
compounds while hepatic, endocrine, and neurologic events are less frequent. 
These side effects are low grade, manageable, and typically resolve within a 
relatively short time frame with a predictable resolution pattern given proper 
management. We therefore propose detailed guidelines for management of major 
immune-related adverse events that are anticipated with antiprogrammed 
death-1/programmed death-ligand 1 therapies based on general experience with 
other monoclonal antibodies and the established management algorithms for 
immune-related adverse events for cytotoxic T-lymphocyte antigen-4 blockade with 
ipilimumab. We anticipate that the antiprogrammed death-1 strategy will become a 
viable and crucial clinical strategy for cancer therapy.