Immunotherapies Could Open the Door for Additional Treatments in Mucosal Melanoma

Despite limited information on treatment options for mucosal melanoma, Richard Joseph, MD, says immunotherapies could be a rewarding challenge for oncologists to undertake in the field.

Joseph, a medical oncologist at Mayo Clinic, says one recent study investigating the immunotherapy nivolumab in the treatment of mucosal melanoma resulted in response rates that could possibly warrant further investigation.

"What they found was that the response rates tended to be slightly lower than what we typically see in cutaneous melanoma, but still a relatively good response rate," he said.

"This gives us, for the time being, some quality data for when we are treating patients with mucosal melanoma. We can now give our patients some good numbers regarding if we should treat them with immunotherapy. Before, we were treating them with immunotherapy without really knowing the efficacy."

The study was based on a pooled analysis of 889 patients, 10% (86) of whom had mucosal melanoma.

At a median follow-up of 9.2 months (0.3-62.5), median progression-free survival (PFS) was 3.0 months (95% CI, 2.2-5.4) for patients with mucosal melanoma and 5.1 months (95% CI, 3.9-6.1) for all treated patients. The objective response rate (ORR) was 23.3% (95% CI, 14.8-33.6) for patients with mucosal melanoma and 35.9% (95% CI, 32.7-39.1) for all treated patients, with complete responses in 6% of patients in both cohorts.

Median duration of response was not reached for patients with mucosal melanoma and was 22.0 months (95% CI, 22.0-NR) for all treated patients. This data marks the first analysis of nivolumab in this subtype and is significant for oncologists treating patients with the disease

Joseph says mucosal melanoma is typically much more aggressive than cutaneous melanoma, generally due to the biology and the late-stage that it often identified.

Roughly 10% of patients usually present with mucosal melanoma as their primary site, and the rates of mutations are also different than cutaneous melanoma, with BRAF mutations less frequently seen and c-KIT mutations more commonly seen.

"Mucosal melanoma is genetically different than cutaneous melanoma. Despite this, we tend to treat them the same without a lot of great evidence to support that. This is an issue.," said Joseph.

With the research into nivolumab in mucosal melanoma, and its possible place in the treatment paradigm, Joseph warns that oncologists must be wary of the unique toxicities immunotherapies may cause.

"The first issue is that toxicities tend to occur longer after the time of administration. With chemotherapies, we see side effects within days and, with immunotherapy, it could be weeks. It doesn’t always quite register with the patients or the doctors that the side effects they might be feeling are related to the treatment they are receiving," said Joseph, adding that these toxicities may be misattributed to different factors, rather than the immunotherapies, due to their late presentation.

"The other challenge is that, while there are resolutions to these symptoms, treatment must be started soon. We can decrease the immune system through immune suppressants, such as steroids. That is very different than managing the toxicities associated with chemotherapy or targeted therapy. We have to get really good at figuring out what dose of steroids to use, when to start, and how quickly to taper. That is a bit of an art."

Looking toward the future of immunotherapies in mucosal melanoma, Joseph says the improvement of the treatment relies on focused research into the field.

"One of the main ways that we could improve on immunotherapy is to focus on further developing the agents we have, rather than just focusing on new drugs. One of the ways we can do that is by determining how long to treat these patients. The duration of therapy is really unknown, especially for patients who are responding," he said.

"Biomarkers are also needed to determine which patients are most likely to respond. There are still a fair number of patients who do not benefit from these treatments, so we need to figure out how to preselect them. We need to also find a biomarker that can help determine when to stop treatment for patients who are already receiving therapy, so that we are not just treating indefinitely."