Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma: a multicenter, retrospective case series. Issue 1 (8th July 2019)

• Record Type: Journal Article
• Authors: LoPiccolo, Jaclyn; Schollenberger, Megan D.; Dakhil, Sumia; Rosner, Samuel; Ali, Osama; Sharfman, William H.; Silk, Ann W.; Bhatia, Shailender; Lipson, Evan J.
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-07-08
• Subjects: Merkel cell carcinoma -- Anti-PD-1-refractory -- Progression -- Immune checkpoint blockers; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0661-6
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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 anti-tumor 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.