Immune cell parameters linked to therapeutic efficacy in advanced renal cell carcinoma
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SAN FRANCISCO — Certain immune cell-related parameters appeared associated with efficacy of immune checkpoint inhibitors among patients with advanced or metastatic clear cell renal cell carcinoma, according to study results.
“These immune cell parameters may represent novel predictive biomarkers for the response to nivolumab and/or nivolumab plus ipilimumab therapy in clear cell [renal cell carcinoma],” Marc-Oliver Grimm, MD, of the department of urology at Jena University Hospital in Germany, said during a presentation at ASCO Genitourinary Cancers Symposium.
Grimm and colleagues employed a tailored approach with nivolumab (Opdivo, Bristol Myers Squibb) and ipilimumab (Yervoy, Bristol Myers Squibb) to identify characteristics of blood-circulating immune cell subsets among patients enrolled in the phase 2 TITAN-RCC trial.
The trial included 207 patients (median age, 65 years; 71% men) with intermediate and poor risk advanced clear cell renal cell carcinoma who received induction therapy with nivolumab once every 2 weeks. Those who experienced early progressive disease (in week 8) or stable or progressive disease at week 16 received two to four “boost” cycles of nivolumab plus ipilimumab. Patients who responded to nivolumab induction went on to receive nivolumab maintenance but could receive nivolumab and ipilimumab for subsequent progressive disease.
Researchers conducted biomarker analyses on blood samples taken at baseline, during induction and during the boost cycles. They used multiparametric flow cytometry to analyze samples from 109 patients treated with first-line therapy and 98 treated with second-line therapy for phenotype and frequency of T-cell, monocyte, myeloid-derived suppressor cell and dendritic cell subsets.
The investigators correlated baseline data with response to nivolumab induction and data from samples taken before the first boost with response to the checkpoint inhibitor combination. They identified associations between treatment response and immune parameters through univariable and multivariable logistic regression modeling.
Results showed responders to nivolumab induction had a higher proportion of T cells expressing 4-1BB+ CD8+ T cells (adjusted OR [aOR] = 1.03; 95% CI, 1.01-1.07), 4-1BB+ CD4+ T cells (aOR = 1.05; 95% CI, 1.02-1.08) or LAG-3+ CD4+ (aOR = 1.03; 95% CI, 1.01-1.05) at baseline compared with nonresponders. In addition, responders to nivolumab-ipilimumab boosts had higher proportions of PD-L1+ CD14+ monocytes (aOR = 1.22; 95% CI, 1.06-1.58), PD-L1+ early-stage myeloid-derived suppressor cells (aOR = 1.14, 95% CI, 1.02-1.41) and PD-L1+ plasmacytoid dendritic cells (aOR = 1.08; 95% CI, 1.01-1.17) vs. nonresponders.
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Grimm M-O, et al. Abstract 367. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco.
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