Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG
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Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG. / Glutsch, Valerie; Schummer, Patrick; Kneitz, Hermann; Gesierich, Anja; Goebeler, Matthias; Klein, Detlef; Posch, Christian; Gebhardt, Christoffer; Haferkamp, Sebastian; Zimmer, Lisa; Becker, Jürgen C; Leiter, Ulrike; Weichenthal, Michael; Schadendorf, Dirk; Ugurel, Selma; Schilling, Bastian.
in: J IMMUNOTHER CANCER, Jahrgang 10, Nr. 11, e005930, 11.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG
AU - Glutsch, Valerie
AU - Schummer, Patrick
AU - Kneitz, Hermann
AU - Gesierich, Anja
AU - Goebeler, Matthias
AU - Klein, Detlef
AU - Posch, Christian
AU - Gebhardt, Christoffer
AU - Haferkamp, Sebastian
AU - Zimmer, Lisa
AU - Becker, Jürgen C
AU - Leiter, Ulrike
AU - Weichenthal, Michael
AU - Schadendorf, Dirk
AU - Ugurel, Selma
AU - Schilling, Bastian
N1 - © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/11
Y1 - 2022/11
N2 - Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95% CI 2.43-not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9% and 26.8 %, respectively. The OS rate at 36 months was 64.3%. Only 3 (21%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.
AB - Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95% CI 2.43-not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9% and 26.8 %, respectively. The OS rate at 36 months was 64.3%. Only 3 (21%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.
KW - Humans
KW - Ipilimumab/pharmacology
KW - Carcinoma, Merkel Cell/drug therapy
KW - Nivolumab/pharmacology
KW - Programmed Cell Death 1 Receptor
KW - Prospective Studies
KW - Skin Neoplasms/drug therapy
KW - Registries
KW - Immune Checkpoint Inhibitors
U2 - 10.1136/jitc-2022-005930
DO - 10.1136/jitc-2022-005930
M3 - SCORING: Journal article
C2 - 36450381
VL - 10
JO - J IMMUNOTHER CANCER
JF - J IMMUNOTHER CANCER
SN - 2051-1426
IS - 11
M1 - e005930
ER -