Dr Verschraegen on Toxicities Associated with Single-agent vs Doublet Immunotherapy in Melanoma

Claire F. Verschraegen, MD, professor of medicine, director of the Division of Medical Oncology, the Ohio State University College of Medicine, Diane Nye and Michael Rayden chair in Innovative Cancer Research, director for translational research, the Ohio State University Comprehensive Cancer Center (OSUCCC) – James, discusses adverse effects (AE) that are commonly associated with the use of single-agent nivolumab (Opdivo) vs the combination of ipilimumab (Yervoy) plus nivolumab in melanoma.

Most patients who receive single-agent nivolumab also experience any-grade AEs, according to Verschraegen. These can range from low-grade, temporary fatigue to chronic autoimmune thyroiditis, Verschraegen begins. The latter toxicity can impact thyroxine, a thyroid hormone that regulates metabolic rate, digestion, heart and muscle function, brain development, and bone health. Notably, a significant decrease in thyroxine levels may require these patients to go on hormone replacement therapy, Verschraegen states.

Similarly, single-agent nivolumab can decrease the secretion of steroids and insulin, leading to hyperglycemia. However, it is rare that this insulin deficiency can trigger the development of new-onset type I diabetes, Verschraegen adds.

Compared with single-agent immunotherapy, the ipilimumab and nivolumab doublet is associated with a higher chance of experiencing toxicities, Verschraegen continues. The risk of severe grade 3 or 4 AEs is particularly pronounced, and increases from about 16% with the single agent to 55% with the doublet, she says. Grade 3 or 4 AEs can necessitate hospitalization or a trip to the emergency room. In this situation, patients would require rapid interventions, Verschraegen explains. Overall, the types of toxicities observed with combination or single-agent immunotherapy are the same, but the risk of chronic AEs does increase with immunotherapy doublets, Verschraegen states.

Although chronic AEs can affect quality of life (QOL) for patients receiving immunotherapy, recent data have shown an improvement in the rate of complete remissions achieved with these classes of drugs , Verschraegen notes. Future investigation is required to determine which AEs could be reversed or better mitigated, as this could improve QOL, Verschraegen concludes.