Technology predicts which melanoma patients will respond to pembrolizumab

UCLA researchers have developed a methodology to predict whether advanced melanoma patients will or will not respond to the breakthrough drug pembrolizumab (Keytruda, Merck).

The FDA approved pembrolizumab for advanced melanoma in September 2014.  Keytruda, according to the FDA, is the first approved drug that blocks the PD-1 cellular pathway, which restricts the immune system from attacking melanoma cells. Keytruda is intended for use following ipilimumab treatment.

READ: FDA approves Keytruda for advanced melanoma

“We’ve had amazing clinical success treating patients battling advanced melanoma with pembrolizumab. The challenge is that it only works in approximately 30 percent of patients with melanoma,” the study’s lead author Paul Tumeh, M.D., assistant professor of dermatology at UCLA, said in a press release. “To address this challenge, we developed an approach that can select for patients that are likely to respond to this therapeutic class.”

Dr. Tumeh and senior author Antoni Ribas, M.D., professor of hematology and oncology at UCLA, studied 46 patients with advanced melanoma treated with pembrolizumab who had undergone tumor biopsies before and during treatment. Over the two year study, they analyzed and classified patients’ biopsies according to whether or not patients responded to pembrolizumab. Researchers then developed an algorithm to predict treatment success or failure.

They tested the algorithm by applying it to 15 other tumor samples from different patients, and correctly predicted outcomes in 13 of those cases.

In an emailed response to Dermatology Times, Drs. Tumeh and Ribas wrote: “Our approach can identify distinct immune cell-types and determine their location and density within tumors. This allows us to understand which immune cell-types become uniquely altered during immunotherapy in patients that respond to therapy vs. patients that progress on therapy.”

What else do dermatologists need to know about this research and how it might impact future treatment?

“Quantitative pathology can determine the expression of multiple proteins within the context of tissue architecture. This will facilitate the identification of distinct immune cell-types that become altered during immunotherapy and the downstream analysis of how these cell-types promote or inhibit tumor rejection. This will become a mainstay approach in melanoma research and in other cancers whose origin is the skin (Merkel cell carcinoma, mycosis fungoides, cutaneous lymphomas) or in cancers that metastasize to the skin,” the doctors write in a correspondence to Dermatology Times. “In the near future, biopsies may be submitted to a laboratory to phenotype the type of tumor and predict whether that patient will respond to a particular treatment.” 

While the authors tell Dermatology Times that they do not have data supporting the application of this platform to other dermatologic diseases, “… it is a high priority to collaborate with physicians and scientists with expertise in diseases such as mycosis fungoides and cutaneous lymphomas, Merkel cell carcinoma, and inflammatory disease states, such as psoriasis. We would be able to understand how the microenvironment of lesions of specific disease evolve during therapeutic intervention in patients that respond vs. patients that progress on a treatment.”

Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. Published online 26 November 2014: doi:10.1038/nature13954