Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses challenges with immunotherapy in patients with Merkel cell carcinoma (MCC).

The 2-year efficacy and safety results from part A of the JAVELIN Merkel 200 study showed that the anti—PD-L1 monoclonal antibody avelumab (Bavencio) induced durable responses and meaningful survival outcomes in patients with metastatic MCC. These findings, which were presented at the 2018 ASCO Annual Meeting, showed a confirmed overall response rate of 33%.

Nghiem says that the next step in metastatic MCC is figuring out how to treat those who do not respond to either chemotherapy or single-agent immunotherapy. There is no go-to or obvious consensus on how these patients should be treated. Additionally, there is no way to predict who will or will not respond to immunotherapy in MCC. That being said, 60% of patients will respond and stay in response to their first-line treatment, so the proportion of patients who do not respond is a relatively small population.

Videos

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses challenges with immunotherapy in patients with Merkel cell carcinoma

Dr. Nghiem on Challenges With Immunotherapy in Merkel Cell Carcinoma

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses response to immunotherapy in Merkel cell carcinoma (MCC).

More than two-thirds of patients with MCC have disease caused by the Merkel cell polyomavirus. These patients have a very low tumor mutational burden (TMB), Nghiem says. The remaining third, which have disease caused by ultraviolet light, have an extremely high TMB. Nghiem says this is interesting because the efficacy of immunotherapy appears to be very similar between the 2 groups.

The dichotomy of causes does not yet seem to signal a difference in response to immunotherapy, Nghiem explains, and patients with both virally-mediated MCC and MCC as a result of sun exposure, can be very immunogenic. There is still a lot to learn, Nghiem adds, as about 50% of all patients with MCC do not respond to immunotherapy.

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses response to immunotherapy in Merkel cell carcinoma. 

Dr. Nghiem on Response to Immunotherapy in Merkel Cell Carcinoma

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses immunotherapy for the treatment of patients with Merkel cell carcinoma (MCC). He presented 2-year efficacy and safety data from the JAVELIN Merkel 200 trial at the 2018 ASCO Annual Meeting.

MCC is considered by many to be a chemotherapy-sensitive disease. Although over 50% of patients will initially respond to chemotherapy, less than 5% will benefit beyond 1 year, Nghiem says. Part A of the single-arm trial focused on the patient population with the biggest need—those who are chemotherapy-refractory.

Patients were treated with the PD-1 inhibitor avelumab (Bavencio). Progression-free survival was 26% after 2 years, and the objective response rate of 33% remained unchanged after a follow-up of 1 year and 18 months. Nghiem says the biggest difference between immunotherapy and chemotherapy is that 70% to 80% of patients stay in response with immunotherapy, according to these data.

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses immunotherapy for the treatment of Merkel cell carcinoma.


Dr. Nghiem on Immunotherapy in Merkel Cell Carcinoma

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine, discusses a phase II trial investigating PD-1 blockade with pembrolizumab as first systemic therapy in patients with advanced Merkel cell carcinoma (MCC).

Adults with advanced, unresectable MCC, good performance status, and those who were not immune suppressed or did not have autoimmune disease were eligible for the trial. Pembrolizumab was administered at 2 mg/kg every 3 weeks. At the time of analysis, which was performed after 12-weeks of treatment, 24 patients had received pembrolizumab and 14 patients had been scanned for signs of disease, explains Nghiem.

Of the 14 evaluable patients, 10 responded to pembrolizumab; representing a 71% response rate, according to Nghiem. These responses consisted of 1 complete response (CR), 1 unconfirmed CR, 4 partial responses (PR), 2 unconfirmed PRs, and 2 progressions. While this data is still early, these results are very promising, especially in such a rare and difficult-to-treat disease, says Nghiem.

Although analysis of PD-L1 expression is still ongoing, Merkel polyomavirus-specific T cells, which are often found in patients with MCC, commonly express inhibitory coreceptors, such as PD-1. Additionally, MCC often expresses PD-L1, suggesting that this rare disease could be highly vulnerable to PD-1 inhibition.

View more from the 2015 European Cancer Congress

Paul Nghiem, MD, PhD, Michael Piepkorn Endowed Chair in Dermatology Research, professor of Dermatology/Medicine at Fred Hutchinson Cancer Research Center, University of Washington Medicine discusses a phase II trial investigating the PD-1 blockade pembrolizumab as first systemic therapy in patients with advanced Merkel cell carcinoma (MCC).

Paul Nghiem, MD, PhD

Articles

Dr. Nghiem on Challenges With Immunotherapy in Merkel Cell Carcinoma

Dr. Nghiem on Response to Immunotherapy in Merkel Cell Carcinoma

Dr. Nghiem on Immunotherapy in Merkel Cell Carcinoma

Dr. Nghiem on Pembrolizumab for Advanced Merkel Cell Carcinoma