Immunotherapy combinations have generated excitement as treatments for patients with melanoma, specifically those involving PD-1 and CTLA-4 inhibitors. A phase I study presented at the 2014 ASCO Annual Meeting that looked at the combination of ipilimumab and nivolumab demonstrated a 2-year overall survival rate of 79%, regardless of BRAF and PD-L1 status, notes Jeffrey S. Weber, MD, PhD. Additionally, the durable objective response rate (ORR) with the combination was 43%.

However, the combination of the agents increased side effects substantially, Weber notes. In the study, 62% of patients reported a grade 3/4 adverse event with the combination. Although the toxicity was higher, most of these side effects were manageable, notes Mario Sznol, MD. The majority of toxicity was similar to what is experienced with ipilimumab, including laboratory abnormalities.

Another exciting combination looked the oncolytic virus T-VEC with ipilimumab, states Omid Hamid, MD. In an 18-patient study, the ORR with the combination was 56% in patients with advanced melanoma. Additionally, the combination was tolerable, with 32% of patients experiencing a grade 3/4 side effect.

Jeffrey A. Sosman, MD, urges caution regarding the exploration of immunotherapy combinations. The addition of ipilimumab to nivolumab increases activity but also brings all of the side effects associated with ipilimumab. Moreover, Sosman notes, the level of single-agent activity seen with PD-1 inhibitors, like nivolumab and pembrolizumab, will be difficult to beat in a randomized trial. However, the combination could have a potential role for patients with PD-L1-negative disease, since these patients responded well to the combination, Sosman notes.