Abstract 1217P
Background
Because therapeutic efficacy of nivolumab (NIVO) in advanced gastric cancer (AGC) is limited, development of new biomarkers and treatment is necessary. Myeloid cells are the major components in the immune system, and reprogramming abnormal myeloid immunity is likely a promising alternative strategy for improving clinical outcomes. However, it remains unclear which subsets in myeloid cells can be targeted for treating AGC, particularly in combination with immune checkpoint inhibitors.
Methods
In AGC patients receiving NIVO, we conducted flow cytometric analysis of fresh peripheral blood cells (PBCs) before and after NIVO treatment. Overall survival (OS) and progression-free survival (PFS) were compared between the high/low groups divided by the spline-based cutoff value of the proportion of each subset in peripheral blood before treatment. This study was supported by ONO PHARMACEUTICAL CO., LTD. and Bristol Myers Squibb.
Results
Of 100 enrolled patients, 91 were included in the analysis. Four unique subsets in the CD11b+ myeloid cells before NIVO treatment showed significant differences in PFS/OS between high and low groups as shown in the table. Table: 1217P
Subset in myeloid cells | group | No of patients | Median PFS [days] (95%CI) | HR (95%CI)P value | Median OS [days] (95%CI) | HR (95%CI)P value |
CD155+ | lowhigh | 3457 | 61 (50 - 129)49 (39 - 62) | 1.49 (0.96 - 2.32)P = 0.073 | 248 (160 - NA)167 (115 - 252) | 1.69 (1.01 - 2.83)P = 0.044 |
CD115+ | lowhigh | 1873 | 303 (165 - NA)170 (140 - 252) | 1.98 (1.16 - 3.37)P = 0.012 | 99 (57 - 210)49.5 (42 -61) | 2.24 (1.15 - 4.37)P = 0.018 |
B7-H3+ | lowhigh | 2665 | 99 (52 - 165)47 (39 - 60) | 2.51 (1.50 - 4.18)P < 0.001 | 393 (153 - NA)167 (140 - 248) | 1.84 (1.05 - 3.23)P = 0.032 |
MARCO+ | lowhigh | 3358 | 64 (50 - 146)48 (39 - 61) | 1.91 (1.20 - 3.04)P = 0.006 | 302 (150 - NA)170 (117 - 252) | 1.75 (1.04 - 2.94)P = 0.036 |
Conclusions
Increase of these four myeloid subsets are associated with poor prognosis in NIVO monotherapy for AGC, suggesting that combination therapy targeting B7H3, MARCO, CD115 or CD155 may be candidates for development of new treatment for AGC.
Clinical trial identification
UMIN IDUMIN000032686.
Editorial acknowledgement
Legal entity responsible for the study
Narikazu Boku.
Funding
Ono Pharmaceutical Co.,Ltd. and Bristol-Myers Squibb.
Disclosure
H. Shoji: Financial Interests, Institutional, Research Grant: Takada Pharmaceutical, Ono Pharmaceutical. N. Boku: Financial Interests, Institutional, Research Grant: Takada Pharmaceutical, Ono Pharmaceutical; Financial Interests, Personal, Other, Honorarium: Ono Pharmaceutical, Bristol-Myers Squibb, Taiho Pharmaceutical, Daiichi Sankyo. K. Nagashima: Financial Interests, Personal, Other, Honorarium: Pfizer, Fujimoto Pharmaceutical, SENJU Pharmaceutical, Toray Industries, Inc.. N. Takahashi: Financial Interests, Personal, Other, Honorarium: Ono Pharmaceutical, Bristol-Myers Squibb, Taiho Pharmaceutical. T. Kawakami: Financial Interests, Personal, Other, Honorarium: Ono Pharmaceutical, Bristol-Myers Squibb. N. Okano: Financial Interests, Personal, Other, Honorarium: Taiho Pharmaceutical, Eli Lilly Japan, Eisai, Bayel, Chugai, Ono Pharmaceutical, Takeda, GlaxoSmithKline. Y. Narita: Financial Interests, Personal, Other, Honorarium: Eli Lilly, Daiichi Sankyo, Taiho, Ono Pharmaceutical, Brstol-Myers Squibb. Y. Yamamoto: Financial Interests, Personal, Other, Honorarium: Takeda, Chugai, Taiho, Sanofi, Yakult, Nihon Servier, Lilly, Asahi Kasei Parma, Ono Pharmaceutical. K. Muro: Financial Interests, Personal, Other, Honorarium: Amgen, AstraZeneca, Ono Pharmaceutical, Chugai, Eli Lilly, Daiichi Sankyo, Taiho, Brstol-Myers Squibb. All other authors have declared no conflicts of interest.