Abstract 1048P
Background
Acral and mucosal melanoma patients may have lower response to aPD1 therapy, providing a unique opportunity to characterize resistance mechanisms.
Methods
This observational study identified 3 groups of acral/mucosal melanoma patients treated by aPD1 monotherapy at a Korean tertiary care hospital: 1) Primary resistance (n=61), 2) Secondary resistance (n=49), 3) Non-progressors (n=14). Pre-treatment and paired pre- and post-treatment biopsies were assayed for PD-L1 IHC, tumor mutational burden (TMB), 18-gene T cell-inflamed gene expression profile (TcellinfGEP) and other key tumor biology and microenvironment mRNA signatures, and immune cell infiltration (CD8+, FOXP3+, CD11c+) by IHC. Descriptive statistics were used to compare non-progressors to resistant patients in baseline samples. Patient-matched paired analysis compared pre-post samples from patients with primary and secondary resistance, adjusting for baseline measurements and TcellinfGEP (GEP) for mRNA signatures.
Results
At baseline, the proportion of PD-L1-positive, TMB-high patients, and median values of GEP, CD8+, FoxP3+, CD11c+ were higher in non-progressors compared to resistant patients overall. At baseline, primary resistant patients had lower values of PD-L1 and GEP compared to secondary resistance, while TMB, CD8, FOXP3, CD11c did not differ. Among resistant patients overall, PD-L1 and GEP increased pre- to post-treatment, while WNT and INFα mRNA signatures decreased. After adjusting for baseline, suggestive differences in changes from pre- to post-treatment values were observed comparing secondary resistance and primary resistance; the change from baseline was lower for gMDSC, and higher for FOXP3+, CD11C+ in secondary compared to primary resistance.
Conclusions
Limitations for this exploratory study include, a relatively small sample size, post-treatment samples unavailable for non-progressors, and variation in post-treatment sample collection time. However, the unique availability of baseline and post-treatment biomarkers provides evidence for potential differences comparing non-progressors and resistant patients as well as for primary and secondary resistance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Merck & Co.
Funding
Merck & Co.
Disclosure
J. Lee: Financial Interests, Personal, Funding: Merck and Co. Inc. X.Q. Liu: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. Q. Zhao: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. K. Kim: Financial Interests, Personal, Funding: Merck. S.T. Kim: Financial Interests, Personal, Funding: Merck and Co. Inc. Y. Sun: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. J. Yearley: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. T. Choudhury: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. A. Webber: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. C. Krepler: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. R. Cristescu: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc. I. Shui: Financial Interests, Personal, Full or part-time Employment: Merck and Co. Inc; Financial Interests, Personal, Stocks/Shares: Merck and Co. Inc; Financial Interests, Personal, Stocks/Shares: Sanofi.