5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome

Background

The NIVOREN GETUG-AFU 26 study reported safety and efficacy of nivolumab in patients with RCC in a “real world setting”. A translational research program was launched to characterize immune cell populations in fresh whole blood at baseline and after 2 months of treatment (C3) to determine association with high-grade toxicity and clinical outcome.

Methods

Absolute number of 106 immune cell populations were analysed in patients treated at a single institution as part of the NIVOREN GETUG-AFU 26 in fresh whole blood using dry formulation panels for multicolor flow cytometry. Predefined clinical endpoints were 6-month grade 3-4 toxicity (treatment related adverse event, TRAE) occurrence and 6-month disease progression occurrence. Missing values were imputed using multivariate imputation by chained equations. Multivariate differential count analysis was done using the DESeq2 R package.

Results

Overall 44 patients were included in this fresh whole blood immune-monitoring. Higher occurrence of grade 3-4 TRAE at 6 months was observed in patients with lower number of CD4⁺PD-1^neg4.1BB⁺ T cell (non-exhausted activated CD4 T cells) counts at baseline (log2 fold change (LFC) = -1.993 95% confidence interval (95%CI)[-2.172; -1.815] ) and with lower number of CD56⁺ T cells (NKT cells) at C3 (LFC = -1.464 _95%CI[-1.597; -1.331]). Higher occurrence of disease progression at 6-month was observed in patients with lower number of CD4⁺PD-1^posCD69⁺ T cells (exhausted activated CD4 T cells) (LFC = -1.186 _95%CI[ -1.308; -1.064 ]) and with higher number of CD4⁺CD244⁺ T cells (exhausted CD4 T cells) (LFC = 1.686 _95%CI[ 1.533; 1.840]) at baseline. No immune cell populations were associated with the occurrence of a 6-month progression during the course of nivolumab (C3).

Conclusions

Fresh whole blood monitoring at baseline and after 2 months of nivolumab identified immune cell populations associated with grade 3-4 TRAE (CD4⁺PD-1^neg4.1BB⁺ T cells and CD56⁺ T cells) and disease progression (CD4⁺PD-1^posCD69⁺ T cells and CD4⁺CD244⁺ T cells). Functional analyses and external validation are ongoing.

Clinical trial identification

NCT03013335.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

Bristol-Myers Squibb.

Disclosure

B. Beuselinck: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS. B. Escudier: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: EUSA; Advisory / Consultancy, Research grant / Funding (institution): Aveo. L. Albiges: Advisory / Consultancy, compensated to institution: Pfizer; Advisory / Consultancy, compensated to institution: Novartis; Advisory / Consultancy, compensated to institution: Roche; Advisory / Consultancy, compensated to institution: Bristol-Myers Squibb; Advisory / Consultancy, compensated to institution: IPSEN; Advisory / Consultancy, compensated to institution: MSD; Advisory / Consultancy, compensated to institution: AstraZeneca. All other authors have declared no conflicts of interest.