81P - Baseline circulating CD4+PD1+high T cells (TCD4PD1H) as predictors of survival in patients (P) with solid tumors treated with immune-checkpoint inhibitors (ICI)

Background

PD1 is an inhibitory receptor exposed on the surface of T cells and other immune cells. In non-small cell lung cancer and melanoma P, as well as after stem cell transplantation, higher levels of CD4+ T cells (TCD4) expressing PD1 (PD1+) correlated with poor survival outcomes. Nonetheless, in vitro PD1 blockade enhanced antitumor immunity. Finally, subpopulations of TCD4 with higher or lower PD1+ levels were identified and associated with differential functional effects and prognosis in follicular lymphoma. We thus aimed at elucidating the prognostic role of peripheral TCD4PD1+ and TCD4PD1H in cancer P treated with ICI-based regimens.

Methods

From 69 consecutive P with solid tumors treated with ICI, we prospectively collected baseline blood samples and evaluated with flow cytometry the proportion (%) of TCD4PD1+ and TCD4PD1H. We performed univariate Cox regressions to detect an association with progression-free survival (PFS) and overall survival (OS). A maximally selected rank statistic method was applied to define a cut-off to identify patients with low and high levels of the specific T cell subpopulation of interest. An association with PFS, OS, and overall response rates (ORR) was then explored according to subgroups. Significance was set at p<0.05.

Results

Median proportion of TCD4PD1+ was 13.9% (interquartile range [IQR]: 9.3–17.4%) and of TCD4PD1H was 0.7% (IQR: 0.3-1.3%). A significant association of TCD4PD1H% levels with OS was observed (hazard ratio [HR]:1.15, p=0.048). A cut-off of 1.1% defined 2 prognostically significant subgroups of P (above and below the threshold, 19 vs. 50 P, respectively). TCD4PD1H_Below vs. TCD4PD1H_Above presented with better PFS (adjusted HR [aHR]: 0.52, 95% confidence intervals [CI]: 0.28 – 0.98, p=0.041), OS (aHR: 0.39, 95%CI: 0.21 - 0.72, p=0.003) and ORR (20.0% vs 0.0%, χ² p=0.035).

Conclusions

Low levels of TCD4PD1H in solid tumors before starting ICI seem to correlate with better ORR, PFS and OS, independently from cancer type, metastatic patterns, P and treatment characteristics. The recruitment of a validation cohort is ongoing, as well as a sub-analysis focused on anti-PD1/antiPDL1.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J. Garcia-Corbacho: Financial Interests, Personal, Advisory Role: Johnson and Johnson Pharmaceutical; Financial Interests, Personal, Project Lead, Local PI: Amgen, Astellas, AstraZeneca, Bayer, Boehringer, Cytomx, Daichii Sankyo, Incyte, Lilly, Menarini, Merck. L. Mezquita: Financial Interests, Personal, Advisory Role: Roche, Roche Diagnostics, Takeda; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Tecnofarma; Financial Interests, Personal, Other, travel/accomodation expenses: Roche, Bristol Myers Squibb. A. Prat: Financial Interests, Personal, Advisory Role: Novartis, Roche, AstraZeneca, BMS, Daiichi Sankyo, Guardant Health, Oncolytics Biotech, Foundation Medicine and Nanostring Technologies. All other authors have declared no conflicts of interest.