KEY TAKEAWAYS
- The NIVOREN phase 2 & PREMIS trial aimed to explore the correlation between CIC expression and clinical outcomes in mRCC patients undergoing IO therapy.
- The result concluded that circulating CD8+ T cells may differentiate responses to dual immunotherapy vs. IO-TKI in mRCC. The role of B cells remains unclear, warranting further investigation, and the study is ongoing.
Immune checkpoint inhibitor (IO) combinations are the norm in metastatic renal cell carcinoma (mRCC), and a deficiency exists in validated biomarkers for directing strategies toward either dual IO or IO combined with tyrosine kinase inhibitors (TKI). Circulating immune cells’ (CIC) potential in informing antitumor immune responses has been primarily studied in IO monotherapy.
Herein, Ronan Flippot and other researchers aimed to explore the correlation between CIC and treatment outcomes in mRCC patients undergoing immunotherapy, including combination regimens.
The study employed flow cytometry to phenotype peripheral blood mononuclear cells before initiating systemic treatment. The CIC subpopulations, including T cells (total CD8+, senescent CD8+, total CD4+, senescent CD4+) and B cells (naive, naive transitional, switched and unswitched memory, double negative, plasmablasts), were examined. Associations between CIC and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed within treatment subgroups. Additionally, an exploratory analysis explored the relationship between CIC and tissue immune infiltrate.
Of 112 patients, the median age was 61, with 75% having clear cell histology and 64% presenting intermediate/poor risk disease. Treatment regimens comprised IO-TKI in 28%, dual IO in 15%, and IO monotherapy in 54% of cases. A decrease in the proportion of CD8+ T cells was linked to enhanced ORR in the overall population (P=0.008), and patients treated with IO monotherapy or dual IO, it correlated with improved ORR (P=0.002) and PFS (HR 0.6, P=0.030). Conversely, no association between T cells and outcomes was noted in patients treated with IO-TKI. Senescent CD8+ T cells exhibited a strong correlation with CD8+ T cell levels (r=0.51, P<0.001) and were inversely associated with the presence of tertiary lymphoid structures or lymphoid aggregates within the tumor.
Among B cells, plasmablasts were inversely associated with ORR (P=0.019) in the overall population without impacting survival. Across treatment regimens, B cell subtypes were predictive only in IO monotherapy, where switched memory B cells were linked to improved ORR (P=0.014) and PFS (HR 0.54, P=0.020).
The result concluded that circulating CD8+ T cells and CD8+ senescence may provide insights into resistance against dual IO but not IO combined with TKI. The involvement of B cells requires further examination. Ongoing longitudinal analyses are in progress.
This study is sponsored by UNICANCER and Gustave Roussy, Cancer Campus, Grand Paris.
Source:
https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trials: https://clinicaltrials.gov/study/NCT03013335
https://clinicaltrials.gov/study/NCT03984318
Flippot R, et al. “Circulating immune cells and activity of immune checkpoint inhibitors in metastatic renal cell carcinoma” Presented at ESMO IO 2023. (Abstract: 23P)
