A pooled analysis of data from studies of ipilimumab in patients with advanced melanoma shows that the immune checkpoint inhibitor can induce lengthy responses, with some patients still alive after nearly 10 years.

The monoclonal antibody ipilimumab (Yervoy; Bristol-Myers Squibb) has had dramatic effects on some patients with advanced melanoma. A new, pooled analysis of survival data provides the longest look yet at efficacy and shows that some patients were still alive nearly 10 years after treatment.

The drug, an immune checkpoint inhibitor that promotes an immune response against tumors, has significantly prolonged survival of patients with advanced melanoma in large phase III clinical trials. Stephen Hodi, MD, associate professor of medicine at Dana-Farber Cancer Institute in Boston, MA, says that “a proportion of patients seem to have a long-term, durable benefit to treatment. We wanted to further characterize the long-term survival with a longer follow-up.”

The results, which Hodi presented on October 2 at the European Cancer Congress in Amsterdam, the Netherlands, assessed data from 1,861 patients in 12 prospective and retrospective studies. The median overall survival was 11.4 months, with 22% of patients alive after 3 years, and 17% after 7 years. No patients died after 7 years, and the longest recorded span of survival so far is 9.9 years. When data were included from an additional 2,985 patients who had been treated with ipilimumab as part of an expanded-access program, the median overall survival was 9.5 months, with a similar survival plateau beginning at around 3 years for 21% of patients.

Vernon Sondak, MD, chief of cutaneous oncology at the Moffitt Cancer Center and Research Institute in Tampa, FL, says that these data help to dispel concerns that the treatment keeps melanoma at bay only temporarily, even for those patients who reached the 3-year mark. Among that group, “it was rare for the melanoma to come back, and there were people almost 10 years out without signs of their melanoma recurring,” he says.

The results are remarkable, Sondak says, given that patients receive only a few intravenous doses of a drug that targets T cells and not the cancer itself. The findings help shift the focus from the question of whether ipilimumab has a long-term effect, to what he says is the larger problem—”how to get more and more people to have the kind of immune response that these patients got.”

Hodi notes that no factors have emerged to explain why a subset of patients responded so dramatically to the therapy while others didn't. “We would love to have a predictive biomarker,” he says, “but we don't have one currently.”

“A lot of research is going on in this area,” Sondak says. Because some people respond to ipilimumab after failing other forms of immunotherapy, either there isn't a single signature to indicate who is likely to respond or the signature can change over time in unpredictable ways, he suggests.