14P - Peripheral immune kinetics in survival prediction of small cell lung cancer patients treated with immune checkpoint blockade therapy

Background

Small cell lung cancer (SCLC) is a lethal neoplasia. Chemotherapy (Ct) plus immune checkpoint blockade therapy (ICBt) is now the standard of care although limited survival benefit. Lack of biomarkers of response leads to suboptimal patient selection, distorting results of clinical trials. Deciphering the ICBt-driven peripheral immune events may recognize those patients who benefit the most. Here, we characterize early peripheral immune kinetics in SCLC patients treated with Ct + ICBt with improved survival.

Methods

SCLC patients from 8 centers were prospectively recruited into 3 cohorts. Cohort 1 include patients treated with Ct (n=24). Cohort 2 (n=37) comprise patients treated with Ct + anti-CTLA-4, and cohort 3 (n=20) patients treated with Ct + anti-PD-1/PD-L1. Peripheral blood mononuclear cells were obtained prior to treatment and after the first dose of ICBt. Variation in proliferation, senescence, adhesion, immunosuppression, and checkpoints markers was assessed by FACS. Kaplan–Meier and log-rank test were used for survival analysis. MaxStat was used to calculate cut points. A p-value <0.05 was considered statistically significant.

Results

We found 6 independent cellular subsets which modulation right after the start of ICBt identify patients with improved survival. An increase in CD8+CD103+Ki67+ cells identify survival benefit in cohorts 1 and 3 (p=0.043; 0.0033). An upregulation of Ki67 in total CD4+ (p=0.012; 0.0027) and CD4+PD-1+ T cells (p=0.026; 0.027), predicts long survival in ICBt cohorts 2 and 3, while a downregulation of CD4+ICOS+ T cells (p=0.025; 0.011) identified survival benefit in these ICBt cohorts. Expansion of Ki67+ and ICOS+ (p=0.0024; 0.0074) CD8+ T cells was also observed in CD8+ T cells from long survivors exclusively from cohort 2.

Conclusions

Expansion of CD8+CD103+Ki67+, CD4+Ki67+, and CD4+PD-1+Ki67+, or a reduction in CD4+ICOS+ circulating T cells subsets identify long survival patients treated with anti-CTLA-4 or anti-PD-1/PD-L1, while an increase in CD8+Ki67+ or CD8+ICOS+ cells predicts benefit only in patients treated with anti-CTLA-4. Assessment of the immune kinetics of these peripheral cellular subsets identify patients who benefit the most from ICBt in SCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fundació Amics de l'Hospital del Mar.

Disclosure

E. Arriola: Financial Interests, Personal and Institutional, Advisory Role, Speaker, Institutional funding, Travel and educational expenses: BMS, MSD; Financial Interests, Personal and Institutional, Advisory Role, Speaker, Institutional and Research funding, Travel and educational expenses: Roche; Financial Interests, Personal and Institutional, Advisory Role, Speaker, Institutional and Research funding: Pfizer; Financial Interests, Personal, Advisory Role, Speaker, Travel and educational expenses: Lilly; Financial Interests, Personal and Institutional, Advisory Role, Speaker, Institutional funding: AstraZeneca; Financial Interests, Personal, Advisory Role, Speaker: Boehringer Ingelheim, Takeda; Other, Personal, Member of Board of Directors, Co-founder: TrialingHealth. All other authors have declared no conflicts of interest.