Abstract 5105
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-1neg4.1BB+ 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-1posCD69+ 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-1neg4.1BB+ T cells and CD56+ T cells) and disease progression (CD4+PD-1posCD69+ 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.
Resources from the same session
2743 - The Impact of Targeted Therapies and Immunotherapy in Melanoma Brain Metastases: a Systematic Review and Meta-Analysis
Presenter: Mario Mandala
Session: Poster Display session 3
Resources:
Abstract
5479 - Intracranial Anti-Tumor Activity in Melanoma Brain Metastases with Encorafenib Plus Binimetinib: A Multicenter, Retrospective Analysis
Presenter: Jose Lutzky
Session: Poster Display session 3
Resources:
Abstract
3560 - Outcomes of Patients with Melanoma Brain Metastases (MBM) Treated with Standard of Care Therapy After Being Excluded from MBM-Specific Clinical Trials
Presenter: Kourtney Holbrook
Session: Poster Display session 3
Resources:
Abstract
3175 - The analysis of current treatment outcomes in melanoma patients with brain metastases
Presenter: Joanna Placzke
Session: Poster Display session 3
Resources:
Abstract
4550 - A multivariate model to define prognostic groups among patients with melanoma brain metastases: a 10-year retrospective cohort study
Presenter: Giacomo Pelizzari
Session: Poster Display session 3
Resources:
Abstract
4191 - The immune landscape of melanoma significantly influences survival in patients with highly mutated tumors.
Presenter: Robert Ferguson
Session: Poster Display session 3
Resources:
Abstract
1625 - Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
Presenter: Kenji Yokota
Session: Poster Display session 3
Resources:
Abstract
5346 - Evaluating polygenic risk score prediction model for melanoma prognosis
Presenter: Miriam Potrony
Session: Poster Display session 3
Resources:
Abstract
5477 - Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Presenter: Maria Grazia Vitale
Session: Poster Display session 3
Resources:
Abstract
3469 - Ancillary evaluation of systemic immune antitumor response (SIAR) and tumor growth rate (TGR) of patients (pts) with metastatic melanoma (MM) treated with radiotherapy (RT) combined with ipilimumab (ipi) in the phase 1 study Mel-Ipi-Rx.
Presenter: Celine Boutros
Session: Poster Display session 3
Resources:
Abstract