TY - JOUR
T1 - Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma
T2 - A multicenter, retrospective case series
AU - Lopiccolo, Jaclyn
AU - Schollenberger, Megan D.
AU - Dakhil, Sumia
AU - Rosner, Samuel
AU - Ali, Osama
AU - Sharfman, William H.
AU - Silk, Ann W.
AU - Bhatia, Shailender
AU - Lipson, Evan J.
N1 - Funding Information:
JL: none. MDS: none. SR: none. OA: none. WHS: Consultant for Bristol-Myers Squibb, Merck, Novartis, Regeneron. Research Funding from Bristol-Myers Squibb, Merck, Novartis. AWS: Consultant for Merck and Bristol-Myers Squibb. Research funding from Biohaven, Bristol-Myers Squibb, Merck, Prometheus, and Viralytics. SB: advisory board participation (with honorarium) from Genentech, EMD-Serono, Sanofi-Genzyme and Bristol-Myers-Squibb (BMS) and research funding to his institution (University of Washington) from Oncosec Medical Inc., EMD-Serono, Merck, BMS, NantKwest and Immune Design. EJL: Consultant for Array BioPharma, Bristol-Myers Squibb, Castle Biosciences, EMD Serono, Macrogenics, Merck, Millennium, Novartis. Research Funding from Bristol-Myers Squibb, Merck, Sysmex. Patent application pending: Method of preventing organ transplant rejections using agonists to the PD-1 checkpoint pathway.
Funding Information:
This study was supported by the Bloomberg∼Kimmel Institute for Cancer Immunotherapy (MDS, WHS, EJL), the Barney Family Foundation (EJL, WHS), Moving for Melanoma of Delaware (MDS, WHS, EJL), The Laverna Hahn Charitable Trust (EJL, WHS), The Roland Park Country School (EJL), and the National Cancer Institute P30 CA006973 (MDS, WHS, EJL).
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/7/8
Y1 - 2019/7/8
N2 - 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.
AB - 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.
KW - Anti-PD-1-refractory
KW - Immune checkpoint blockers
KW - Merkel cell carcinoma
KW - Progression
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U2 - 10.1186/s40425-019-0661-6
DO - 10.1186/s40425-019-0661-6
M3 - Article
C2 - 31287031
AN - SCOPUS:85068869711
VL - 7
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
SN - 2051-1426
IS - 1
M1 - 170
ER -