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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract