Predicting the response to PD-1/PD-L1 immune checkpoint blockade in patients with metastatic melanoma remains challenging. In this study, we have investigated for the relationships between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. We studied the formalin-fixed paraffin-embedded tumor samples of 36 patients with metastatic melanoma using PD-L1 immunohistochemistry (IHC) and PD-L1/chromosome 9 fluorescent in situ hybridization (FISH). PD-L1 IHC was positive in 3 patients (8.33%, with >5% stained tumor cells) and PD-L1 FISH test revealed 5 (13.8%) PD-L1 amplifications, 8 (22.2%) PD-L1 gains, and 2 (5.5%) PD-L1 losses. Among 14 responders and 13 nonresponders to anti-PD-1 immunotherapy, we concluded that there was no significant relationship between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. In our study, the determination of PD-L1 expression using IHC and PD-L1 copy number using FISH was insufficient to predict the response to PD-1/PD-L1 immune checkpoint blockade in patients with advanced melanomas.
As of March 2021, analysis of 92 patients had been finalized.Patients older than 60 years had a significantly lower TCR repertoire diversity compared to younger (p = 0.03, Wilcoxon rank sum test).There was no association between lymphoma subtype and TCR repertoire diversity. In a Kaplan-Meier survival analysis we found a trend towards longer overall survival in patients with high TCR repertoire diversity (Figure 1). Detailed profiling of the TCR repertoire coupled with long term follow-up of patients undergoing ASCT may provide novel information regarding the impact of the patient's own adaptive immune response on treatment efficacy. A dysfunctional T-cell repertoire can furthermore have implications for selection of patients to undergo cellular therapies (ie. ASCT or CAR T-cell treatment) in contrast to non-cellular therapies (i.e. bispecific antibodies, small molecule inhibitors). Full analysis of all 288 patients and correlation with post-transplant infections, transfusions and secondary cancers are ongoing and will be presented at the 16-ICML.
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