Abstract 2901
Background
Anti-PD-1 antibodies represent nowadays a first-choice therapy for metastatic melanoma patients. Despite impressive results in terms of PFS and OS, a proportion of patients does not respond to anti-PD-1 therapy with an overall poor prognosis. Identification of predictive biomarkers is considered an important unmet clinical need to avoid expensive and potentially harmful drugs in patients who will not respond to them. In the last years, many studies have evaluated the role of cytokines on both blood and tissue samples as predictive biomarkers for immunotherapy, with encouraging results.
Methods
Blood samples from 18 patients with metastatic melanoma treated with anti-PD-1 antibodies as first line therapy were collected at baseline. 8 patients were classified as non-responders (best response: PD excluding pseudo-progression with median PFS of 2 months) and 10 patients as responders (best response: PR or CR, with median PFS of 17 months). mRNA expression levels of the main pro- and anti-inflammatory cytokines were evaluated by Real time quantitative PCR in PBMCs obtained from baseline blood samples. Unpaired two-tailed t-test was used for statistical analysis.
Results
IFN-γ mRNA expression levels were higher in responder patients (p < 0.01) whereas IL-10 levels tended to be higher in non-responders (p > 0.05). Combining data for each patient, we noticed a correlation between higher levels of IFN-γ and lower levels of IL-10 for responders and vice versa. Starting from these findings, we observed that the IFN-γ/IL-10 ratio was higher (median: 43,3 vs 5,2) in responders (p < 0.01), with high negative and positive predictive value (NPV:100% and PPV:91% using a threshold of 18). The main lymphocyte subpopulations producing these cytokines were also identified.
Conclusions
Our data suggest an interesting correlation between IFN-γ/IL-10 ratio and response to anti-PD-1 therapy in melanoma patients. This correlation seems to be stronger than using IFN-γ expression levels alone probably because of the influence of anti-inflammatory cytokines. Since this is an exploratory and retrospective analysis of 18 patients, a larger population should be tested to validate our results.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Dipartimento di Medicina di Precisione, Università degli studi della Campania Luigi Vanvitelli.
Funding
Has not received any funding.
Disclosure
F. Ciardiello: Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Servier; Advisory / Consultancy: BMS; Advisory / Consultancy: Cellgene; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Takeda. T. Troiani: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bayer. All other authors have declared no conflicts of interest.
Resources from the same session
2507 - KEYLYNK-010: Phase 3 Study of Pembrolizumab (pembro) Plus Olaparib (OLA) vs Enzalutamide (ENZA) or Abiraterone (ABI) in ENZA- or ABI-Pretreated Patients (pts) With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Had Progression on Chemotherapy (CTx)
Presenter: Evan Yu
Session: Poster Display session 3
Resources:
Abstract
2944 - PROSTRATEGY: A Spanish Genitourinary Oncology Group (SOGUG) multi-arm multistage (MAMS) phase III trial of immunotherapy strategies in high-volume metastasic hormone-sensitive prostate cancer.
Presenter: Jose Arranz Arija
Session: Poster Display session 3
Resources:
Abstract
3535 - A phase 1 study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Ben Tran
Session: Poster Display session 3
Resources:
Abstract
4951 - ProBio: An outcome-adaptive, multi-arm, open-label, multiple assignment randomised controlled biomarker-driven trial in patients with metastatic castration-resistant prostate cancer (EudraCT: 2018-002350-78, NCT03903835)
Presenter: Johan Lindberg
Session: Poster Display session 3
Resources:
Abstract
2892 - A phase 3 randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (NCT03748641)
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
2427 - The Extended/Phase II Study of Safety And Tolerability Of Proxalutamide (GT0918) In Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Who Failed Either Abiraterone (Abi) Or Enzalutamide (Enza)
Presenter: Nicholas Vogelzang
Session: Poster Display session 3
Resources:
Abstract
3224 - Addition of an oral docetaxel treatment (ModraDoc006/r) to androgen deprivation therapy (ADT) and intensity-modulated radiation therapy (IMRT) in patients with high risk N+M0 prostate cancer
Presenter: Marit Vermunt
Session: Poster Display session 3
Resources:
Abstract
3312 - A phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy with LHRH agonist or antagonist versus anti-androgen therapy with apalutamide in patients with biochemical progression after radical prostatectomy.
Presenter: Piet Dirix
Session: Poster Display session 3
Resources:
Abstract
2829 - Health-Related Quality of Life (HRQoL) and Updated Follow-Up From KEYNOTE-057: Phase 2 Study of Pembrolizumab (pembro) for Patients (pts) With High-Risk (HR) Non–Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guérin (BCG)
Presenter: Ronald de Wit
Session: Poster Display session 3
Resources:
Abstract
2673 - Clinical activity of vofatamab (V), an FGFR3 selective antibody in combination with pembrolizumab (P) in metastatic urothelial carcinoma (mUC), updated interim analysis of FIERCE-22
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract