Abstract 109P
Background
Most patients (pts) with advanced cancer do not benefit from immunotherapy (IT) and no predictive and reliable biomarker exists across cancer-types. Here, we studied lymphocyte subpopulations on peripheral blood as easily quantifiable biomarkers of response to IT.
Methods
From 11/2016 to 06/2019, pts with advanced solid cancer treated with IT at Hospital Clinic Clinical Trials Unit were recruited. Blood samples were collected at baseline (C1D1), at day 1 of cycle 2 (C2D1) and at each radiologic evaluation. Flow cytometry analyses were performed using the lineage and differentiation markers CD25, CD3, FOXP3, CD40L, HLA-DR, CD4, CD62L, CD69, CD8, CTLA4, CD19, CD16/56, CD28, PDL1, PD1, CD45RO/RA and CCR7. Forty-four lymphocyte subpopulations (LSP) were identified and quantified. The primary objective was to associate the levels of LSP with response according to iRECIST criteria. Secondary objectives were progression-free survival (PFS) and overall survival (OS). Cox models, logistic regressions, and areas under the ROC (AUC) were performed. Adjustment for multiple comparisons was considered.
Results
71 evaluable pts with non-small cell lung cancer (25%), colorectal (15%), breast (12%), head and neck (10%), bladder (8%), melanoma (7%), renal (5%), prostate (5%) and others (10%) were recruited. Median age was 62 (22-80), 63% of pts were male and 90% were immune naïve. 50 pts received anti-PD1 (71%) and 69% of ITs were given as monotherapy. The overall response rate (ORR) was 13.5% (95% CI 8-22%). At C1D1, no LSP was found associated with ORR. At C2D1 (n=61) higher levels of effector memory T cells (TEM: CD3+CD45RO+CCR7-) were found associated with response (AUC=0.81, 100% sensitivity, 59.6% specificity, PPV 27.6% and NPV 100%), PFS and OS. The ORR in high-TEM (above median) was 26.7% vs 0% in low-TEM. Compared to low-TEM, high-TEM (above median) was associated with improved PFS (hazard ratio [HR]=0.23; p<0.001) and OS (HR=0.33; p=0.003). All associations were independently of cancer-type, sex, type of immunotherapy and immune-naïve state.
Conclusions
Levels of peripheral blood effector memory T-cells during IT might help predict response across cancer-types. Further characterization and validation of this LSP is ongoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Medical Oncology and Immunology departments at Hospital Clinic Barcelona.
Funding
Has not received any funding.
Disclosure
J. Garcia-Corbacho: Speaker Bureau/Expert testimony: Bayer; Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Solti; Honoraria (institution), Clinical Trials: MSD; Honoraria (institution), Clinical Trials: Amgen; Honoraria (institution), Clinical Trials: BMS; Honoraria (institution), Clinical Trials: Novartis; Honoraria (institution), Clinical Trials: Bayer; Honoraria (institution), Clinical Trials: Astellas; Honoraria (institution), Clinical Trials: Boeringher Ingelheim; Honoraria (institution), Clinical Trials: Cytomx; Honoraria (institution), Clinical Trials: Pfizer; Honoraria (institution), Clinical Trials: Tesaro. N. Vinolas Segarra: Honoraria (self): Roche; Honoraria (self): Boeringher Ingelheim; Honoraria (self): Pierre-Fabre; Travel/Accommodation/Expenses: BMS; Honoraria (self): Lilly; Honoraria (self): AstraZeneca. B. Mellado: Research grant/Funding (self): Astellas; Research grant/Funding (institution): Jansen; Non-remunerated activity/ies: Sanofi; Research grant/Funding (institution): Roche; Non-remunerated activity/ies: BMS; Honoraria (self): Merck; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer. J. Maurel: Honoraria (self): Sirtex; Honoraria (self): Servier; Honoraria (self): Pierre Fabre; Honoraria (self): Advance Medical; Honoraria (self): Shire; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Sanofi; Honoraria (self): Roche; Honoraria (institution): Merck; Honoraria (self): Amgen; Honoraria (institution): Biocartis; Honoraria (institution): Nanostring; Honoraria (institution): Incyte. L. Gaba: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Tesaro; Honoraria (self): GSK. N. Baste: Advisory/Consultancy: Merck; Advisory/Consultancy: BioNtech; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: BMS; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Eisai. N. Reguart: Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Boeringher Ingelheim; Speaker Bureau/Expert testimony: Guardant Health; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Abbie; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Amgen; Honoraria (institution), Clinical Trials: MSD; Honoraria (institution), Clinical Trials: BMS; Honoraria (institution), Clinical Trials: Roche; Honoraria (institution), Clinical Trials: Boeringher Ingelheim; Honoraria (institution), Clinical Trials: Pfizer; Honoraria (institution), Clinical Trials: Abbvie; Honoraria (institution), Clinical Trials: Novartis; Honoraria (institution), Clinical Trials: AstraZeneca; Honoraria (institution), Clinical Trials: Takeda; Honoraria (institution), Clinical Trials: Amgen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer. A. Prat: Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony: Nanostring technologies; Leadership role, Member Executive Board Breast International Group (BIG): BIG; Leadership role, Member of the Board Solti's Foundation: Solti Foundation; Leadership role, Patronage committee: Actitud Frente al Cancer Foundation; Leadership role, Member Executive Board: SOLTI; Honoraria (institution), Contracted Research, Clinical Trials: Boeringher Ingelheim; Honoraria (institution), Clinical Trials: Lilly; Honoraria (institution), Contracted Research, Clinical Trials: Roche; Honoraria (institution), Contracted Research: Pfizer; Honoraria (institution), Contracted Research, Clinical Trials: Nanostring technologies; Honoraria (institution), Clinical Trials: Novartis; Honoraria (institution), Clinical Trials: Amgen; Honoraria (institution), Clinical Trials: Daiichi Sankyo; Honoraria (institution), Contracted Research: Roche Farma SA; Honoraria (institution), Contracted Research: Sysmex Europa GmbH; Honoraria (institution), Contracted Research: Medica Scientia inno, research, SL; Honoraria (institution), Contracted Research: Celgene, SLU; Honoraria (institution), Contracted Research: Astellas Pharma, SA. All other authors have declared no conflicts of interest.