Research Fellow 1. Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France, Ile-de-France, France
Background: Immune Checkpoint Blockade (ICB) can result in sustained response in metastatic renal cell carcinoma (mRCC) patients, but no reliable biomarker of outcomes is validated. We previously reported an association between IgM memory B cell subpopulation and outcomes in patients treated with single-agent nivolumab. Herein, we explored B cell subpopulations and outcomes in an independent patient cohort treated with ICB, including combinations.
Methods: Immune phenotyping on fresh whole-blood samples was performed by flow cytometry at baseline in the PREMIS trial (NCT03984318). Populations explored included total circulating B cells, naive B cells, double negative B cells, and memory B cells, including switched (IgG+) and unswitched (IgM+). Optimal cutoffs for outcome determination were defined by ROC curve analysis, and survival was estimated by the Kaplan-Meier method.
Results: Twenty patients were enrolled, including 14 treated with ICB combinations and 6 with ICB monotherapy. Almost all patients (80%) had clear cell histology and 65% were treated in first-line setting. Most patients had International mRCC Database Consortium risk groups of poor (25%) or intermediate (55%).In this analysis, the number and proportion of total B cells were not associated with survival. Among B cells subpopulations, however, there was a trend for longer PFS in patients harboring higher IgM memory B cells, with median PFS of 13.8 months, compared to 2.9 months, hazard ratio 0.36 (95% CI, 0.13-0.98), p = 0.08. Other B cells subpopulations were not associated with PFS. There was no significant association with response rate or overall survival.
Conclusions: In this small cohort study, elevated circulating IgM memory B cells were numerically associated with longer PFS in patients treated with ICB for mRCC, including combinations. These findings warrant further exploration of B cell subpopulations in larger, more homogeneous cohorts.