TY - JOUR
T1 - Therapeutic benefits of Ipilimumab among Japanese patients with Nivolumab-refractory mucosal melanoma
T2 - A case series study
AU - Saijo, Ken
AU - Imai, Hiroo
AU - Ouchi, Kota
AU - Okada, Yoshinari
AU - Sato, Yuko
AU - Komine, Keigo
AU - Takahashi, Masahiro
AU - Takahashi, Shin
AU - Shirota, Hidekazu
AU - Takahashi, Masanobu
AU - Ishioka, Chikashi
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The antibodies targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have provided survival benefits in patients with advanced malignant melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab are considered superior to the anti-CTLA-4 antibody ipilimumab as first-line therapy, suggesting that ipilimumab should be administered to patients with anti-PD-1 antibodyrefractory melanoma in the second-line setting. However, there is limited evidence regarding the efficacy and safety of ipilimumab after disease progression on anti-PD-1 antibody therapy. Moreover, in patients with mucosal melanoma, a rare and aggressive subtype, evidence is extremely poor. This study aimed to clarify the efficacy and safety of ipilimumab among Japanese patients with nivolumab-refractory advanced mucosal melanoma. We retrospectively analyzed the seven patients with advanced mucosal melanoma who were treated with ipilimumab after disease progression on nivolumab at our hospital between September 2015 and December 2017. No patient achieved complete response or partial response to ipilimumab therapy. However, six patients achieved stable disease, and of these patients, three achieved a decline in the tumor size. All the three patients with a decline in tumor size developed grade 3 toxicity: Two patients developed colitis and one patient experienced alanine aminotransferase elevation. The median progression-free survival (PFS) for prior nivolumab therapy was 148 days. The median PFS for ipilimumab therapy after disease progression with nivolumab was 193 days. The median overall survival was 661 days. In conclusion, although even partial response was undetectable with ipilimumab therapy, ipilimumab could produce additional PFS among nivolumab-refractory advanced mucosal melanoma patients.
AB - The antibodies targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have provided survival benefits in patients with advanced malignant melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab are considered superior to the anti-CTLA-4 antibody ipilimumab as first-line therapy, suggesting that ipilimumab should be administered to patients with anti-PD-1 antibodyrefractory melanoma in the second-line setting. However, there is limited evidence regarding the efficacy and safety of ipilimumab after disease progression on anti-PD-1 antibody therapy. Moreover, in patients with mucosal melanoma, a rare and aggressive subtype, evidence is extremely poor. This study aimed to clarify the efficacy and safety of ipilimumab among Japanese patients with nivolumab-refractory advanced mucosal melanoma. We retrospectively analyzed the seven patients with advanced mucosal melanoma who were treated with ipilimumab after disease progression on nivolumab at our hospital between September 2015 and December 2017. No patient achieved complete response or partial response to ipilimumab therapy. However, six patients achieved stable disease, and of these patients, three achieved a decline in the tumor size. All the three patients with a decline in tumor size developed grade 3 toxicity: Two patients developed colitis and one patient experienced alanine aminotransferase elevation. The median progression-free survival (PFS) for prior nivolumab therapy was 148 days. The median PFS for ipilimumab therapy after disease progression with nivolumab was 193 days. The median overall survival was 661 days. In conclusion, although even partial response was undetectable with ipilimumab therapy, ipilimumab could produce additional PFS among nivolumab-refractory advanced mucosal melanoma patients.
KW - Anti-CTLA4 antibody
KW - Anti-PD-1 antibody
KW - Immune checkpoint inhibitor
KW - Immune-related adverse event
KW - Mucosal melanoma
UR - http://www.scopus.com/inward/record.url?scp=85066412296&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066412296&partnerID=8YFLogxK
U2 - 10.1620/tjem.248.37
DO - 10.1620/tjem.248.37
M3 - Article
C2 - 31105123
AN - SCOPUS:85066412296
VL - 248
SP - 37
EP - 43
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 1
ER -