Journal
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Volume 7, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s40425-019-0661-6
Keywords
Merkel cell carcinoma; Anti-PD-1-refractory; Progression; Immune checkpoint blockers
Categories
Funding
- Bloombergsimilar toKimmel Institute for Cancer Immunotherapy
- Barney Family Foundation
- Moving for Melanoma of Delaware
- Laverna Hahn Charitable Trust
- Roland Park Country School
- National Cancer Institute [P30 CA006973]
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Merkel cell carcinoma (MCC) is a rare but clinically aggressive cancer with a high mortality rate. In recent years, antibodies blocking the interactions among PD-1 and its ligands have generated durable tumor regressions in patients with advanced MCC. However, there is a paucity of data regarding effective therapy for patients whose disease is refractory to PD-1 pathway blockade. This retrospective case series describes a heterogeneous group of patients treated with additional immune checkpoint blocking therapy after MCC progression through anti-PD-1. Among 13 patients treated with anti-CTLA-4, alone or in combination with anti-PD-1, objective responses were seen in 4 (31%). Additionally, one patient with MCC refractory to anti-PD-1 and anti-CTLA-4 experienced tumor regression with anti-PD-L1. Our report - the largest case series to date describing this patient population - provides evidence that sequentially-administered salvage immune checkpoint blocking therapy can potentially activate antitumor immunity in patients with advanced anti-PD-1-refractory MCC and provides a strong rationale for formally testing these agents in multicenter clinical trials. Additionally, to the best of our knowledge, our report is the first to demonstrate possible anti-tumor activity of second-line treatment with a PD-L1 antibody in a patient with anti-PD-1-refractory disease.
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