1286P - Senescent immune phenotype (SIP) status predicts resistance to immune checkpoint blockers (ICB) among CMV+ advanced non-small cell lung cancer (aNSCLC) patients

Background

Immunosenescence is a progressive remodeling of immune functions with a multifactorial etiology (aging, chronic inflammation, persistent infections, cancer). CMV has been shown to act as chronic antigenic stressor and to accelerate immune ageing by affecting peripheral blood T cell phenotypes, including loss of CD28 or overexpression of CD57. We defined a SIP as the proportion of CD28^–CD57⁺KLRG1⁺CD8⁺ circulating T cells. We showed that a high pretreatment SIP (>39.5%, SIP+) was associated with resistance to ICB in patients with aNSCLC. We aimed to assess the role of SIP combined to CMV status on ICB outcomes in aNSCLC patients.

Methods

Baseline SIP status was assessed by flow cytometry on fresh blood samples from ICB-treated aNSCLC patients. CMV serology was determined by enzyme immunoassay. Overall survival (OS) and progression-free survival (PFS) curves were estimated with the Kaplan-Meier method and compared by the logrank test.

Results

95 aNSCLC patients treated with ICB [43% 1^st line; 57% ≥ 2 lines] were evaluable for SIP: 75% had a disease progression, 21% were SIP+, SIP median value was 21.9% (min 0%, max 68.9%), and median age was 64.1 years. Median PFS and OS were 3.8 and 13 months respectively. Among 92 patients evaluable for CMV status, 58% were CMV-positive (CMV+). As expected, median PFS was significantly lower in SIP+ (2.45 vs 4 months, p=0.0271) and median OS was lower in SIP+ (7.4 vs non reached, p=0.0618) compared to SIP- patients. CMV+ patient’s rate was significantly higher in SIP+ compared to SIP- patients (94.4% vs 48.6%, p=0.0003). CMV status was not sufficient to predict outcomes (Median PFS CMV+ patients 3 vs 5.2 months in CMV-, p=0.1606). Among CMV+, SIP+ patients represent only 32.1%; these SIP+ patients had lower PFS (1.9 vs 3.3 months, p=0.0401) and OS (6.2 months vs non reached, p=0.0736) than SIP-.

Conclusions

CMV+ status is associated with SIP phenotype, SIP+ identifies patients with poorer outcomes in CMV+ aNSCLC.

Clinical trial identification

NCT03984318.

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy, Cancer Campus, Grand Paris.

Funding

Malakoff Médéric.

Disclosure

B. Duchemann: Non-Financial Interests, Institutional, Other: Roche; Non-Financial Interests, Institutional, Other: Oxyvie; Non-Financial Interests, Institutional, Other: Pfizer; Non-Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Institutional, Other: MSD; Financial Interests, Institutional, Other: BMS; Financial Interests, Institutional, Other: Chiesi. N. Chaput: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Cytune Pharma. All other authors have declared no conflicts of interest.