1475P - Torque teno virus DNA load as biomarker for tumor response to mono immune checkpoint inhibition in non-small cell lung cancer

Background

The ubiquitous Torque Teno Virus (TTV) in serum may reflect immune status and is used clinically as a biomarker of immunosuppression in solid organ recipients. Its ability to reflect functional T-cell activity as a measure of immune suppression may be applicable in lung cancer patients as well, considering the role of tumor induced immunosuppression in these patients. We hypothesize that TTV DNA load, or its change early in treatment, may reflect response to mono immune checkpoint inhibition (ICI) with a PD-1 inhibitor.

Methods

This retrospective, exploratory study included patients with non-small cell lung cancer (NSCLC) who started treatment with pembrolizumab or nivolumab between 2014 and 2022. Patients were selected on durable response (≥6 months response or stable disease) and non-response (progressive disease as best response), and were divided into two equal groups. Subsequently, TTV DNA load was measured quantitively on prospectively collected plasma samples via the OncoLifeS biobank. TTV DNA load at baseline was compared, as well as change in TTV DNA load after 4-6 weeks to baseline.

Results

A total of 63 patients were included, 31 responders and 32 non-responders. Median progression free survival (mPFS) was 193 weeks [IQR 50 weeks – not reached] vs 6 weeks [IQR 5 –6 weeks]. Responders were slightly younger (median 64 vs 70 years, p=0.05) and had a better performance status (PS 0 in 58% vs 25%, p=0.03), all other baseline characteristics were comparable. TTV DNA load at baseline was above the threshold in 44 patients (70%). Median TTV DNA load was 2.77 log copy numbers/mL (cp/mL) [IQR 2.13 – 3.27] in responders and 3.25 cp/mL [IQR 2.26 – 2.80] in non-responders, p=0.173. Change in TTV DNA load after 4-6 weeks compared to baseline was -0.13 cp/mL [IQR-1.73 – 0.10] in responders vs -0.33 [IQR -1.61 – 0.20] in non-responders (p=0.833). Cox-regression analysis, adjusted for sex, age and PS, showed no correlation between change in TTV DNA load, and mPFS and overall survival.

Conclusions

Level of immune suppression in this cohort of NSCLC patients measured by TTV DNA load, either at baseline or change after 4-6 weeks after mono ICI, was not associated with tumor response or survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

European Union’s Horizon 2020 research and innovation program [grant number 875171].

Disclosure

B. Muntinghe: Other, Personal, Other, Travel grant, outside the submitted work: 2022 AACR-Bristol Myers Squibb Scholar-in-Training Award. E. Suazo Zepeda: Financial Interests, Institutional, Other, Research scholarship, [Grant No 1074186]: Mexico's National Council of Science and Technology (CONACYT). H. Kievit: Financial Interests, Institutional, Other, Research scholarship, outside submitted work: Roche; Financial Interests, Institutional, Other, Travel grant, outside submitted work: Mundipharma. A.J. Van Der Wekken: Financial Interests, Institutional, Research Funding, Outside submitted work: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Takeda; Financial Interests, Institutional, Advisory Board, Outside submitted work: Janssen Cilag; Financial Interests, Institutional, Other, Personal fee, outside submitted work: Lilly, Amgen, Merck. E. Schuuring: Financial Interests, Institutional, Advisory Board: MSD/Merck, AstraZeneca, Astellas Pharma, Roche, Illumina, Agena Biosciences, Lilly, Jansen Cilag, CC Diagnostics, Amgen, GSK, Novartis, Bayer; Financial Interests, Institutional, Invited Speaker: Biocartis, Illumina, Agena Biosciences, BioRAD, Lilly, SeraCare/LGT, Jansen Cilag; Financial Interests, Institutional, Research Grant, ZonMw: Predictive Analysis for Therapy: PATH to Optimizing Access to Personalised Cancer Therapy in the Netherlands; from Tissue to Therapy: Abbott, CC Diagnostics; Financial Interests, Institutional, Research Grant, ctKRAS testing using BioRad ddPCR in cfDNA from plasma as a predictive biomarkers for tumor response to Nivolumab in KRAS-mutated non-small cell lung cancer: BioRad; Financial Interests, Institutional, Research Grant, EU-IHI-Horizon: GUIDE.MRD - GUIding multi-moDal thErapies against MRD by liquid biopsies – steering committee/WP-leader: BMS; Financial Interests, Institutional, Funding, Roche/Ventana: Validation and implementation of pan-TRK immuno staining and RNA-based NTRK-fusion detection in a diagnostic setting: Roche; Financial Interests, Institutional, Research Grant, B-IO - Unraveling tumor response and resistance to combined chemotherapy and PD-L1 inhibition with minimal invasive techniques in patients with advanced NSCLC with targetable disease: Roche; Financial Interests, Institutional, Research Grant, ALPINE-study - Identification of resistant mechanisms in progressing lung cancer patients with an initial tumor response or with stable disease on immunotherapy using comprehensive ultrasensitive NGS biomarker analysis: Roche; Financial Interests, Institutional, Research Grant, CLINBASE - validation and implementation of Agena UltraSEEK using plasma cfDNA samples from NSCLC patients: Agena Biosciences; Financial Interests, Institutional, Research Grant, Alpe d’HuZes/KWF/ Agena Biosciences: GALLOP-11 study - treatment of gastrointestinal stromal tumors based on serial mutation analysis of circulating tumor DNA – WP-leader: Agena Biosciences; Financial Interests, Institutional, Research Grant, De validatie van Illumina’s TSO500 NGS panel voor DNA-analyse van HRD-genen in het kader van diagnostiek van prostaatkanker - (mede) projectleider: AstraZeneca; Financial Interests, Institutional, Research Grant, Evaluation of CIN2+ specific methylation markers as triage testing optimizing referral to gynecologist for colposcopy after primary hrHPV-positive test in the new Dutch population-based screening program - (mede) projectleider: CC Diagnostics; Financial Interests, Institutional, Research Grant, Imalife/Siemens: NEO-PUSH study - cfDNA from whole blood to detect lung cancer in high risk group of Imalife patients undergoing ULD-CT screening - (mede) projectleider: Siemens; Financial Interests, Institutional, Research Grant, Implementatie Invitae-ArcherDX fusiegendetectie tbv NTRK diagnostiek - (mede) projectleider: Archer/Bayer/Invitae; Non-Financial Interests, Advisory Role: ZINL (Health Care Agency). J.T.J.N. Hiltermann: Financial Interests, Institutional, Research Funding, Outside submitted work: AZD, Roche, BMS; Financial Interests, Institutional, Advisory Role, Outside submitted work: MSD, Roche, AZD, BMS. All other authors have declared no conflicts of interest.