Peripheral blood T-cell receptor immune repertoire characterization of resectable stage IIIA non-small cell lung cancer patients receiving neo-adjuvant chemo-immunotherapy treatment from NADIM study.

Authors

null

Alberto Cruz Bermudez

Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain

Alberto Cruz Bermudez , Marta Casarrubios , Raquel Laza Briviesca , Belen Sierra-Rodero , Miguel Barquin , Atocha Romero , Fernando Franco , Virginia Calvo , Ernest Nadal , Amelia Insa , Rosario Garcia-Campelo , Joaquin Casal , Manuel Domine , Bartomeu Massuti , Margarita Majem , Delvys Rodriguez-Abreu , Alex Martinez-Marti , Javier De Castro , Mariano Provencio-Pulla

Organizations

Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, Liquid Biopsy Laboratory, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, Department of Medical Oncology, University Hospital Puerta de Hierro-Majadahonda, Madrid, Spain, Institut Català d’Oncologia, L’Hospitalet, Barcelona, Spain, Hospital Clinico Universitario de Valencia, Valencia, Spain, University Hospital A Coruña, A Coruña, Spain, Complexo Hospitalario de Vigo, Vigo, Spain, Oncology Department and Translational Oncology Division, University Hospital Fundacion Jimenez Diaz, Madrid, Spain, Alicante University Hospital ISABIAL, Alicante, Spain, Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Hospital Universitario Insular de Gran Canaria, Las Palmas De Gran Canaria, Spain, Medical Oncology Department, Vall d´Hebron University Hospital/Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain, Translational Oncology Unit at Medical Oncology Division, Hospital Universitario La Paz, IdipAZ, Madrid, Spain

Research Funding

Pharmaceutical/Biotech Company
BRISTOL MYERS SQUIBB

Background: Characterization of the peripheral blood T-cell receptor (TCR) repertoire has become a novel approach to predict the clinical benefit to anti-PD1/PDL1 therapy. However, there is lack of knowledge about the clinical relevance of TCR repertoire in terms of pathological response and clinical outcomes (PFS and OS) in chemo-immunotherapy. To answer this question we have analysed samples from the NADIM study (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab. Methods: Using ION Torrent-based next-generation sequencing we have analysed TCR repertoire of peripheral blood from 30 patients receiving chemo-immunotherapy. Using 25ng of total RNA from PBMCs, clonal convergence, evenness and diversity were calculated at diagnosis (pre-treatment) and after 3 cycles of Nivolumab plus carboplatin (post-treatment). Regarding pathological responses, patients were classified in 3 groups: complete response (pCR) (0% viable tumour at the resection specimen), mayor response (pMR) ( < 10% viable tumour) and incomplete response (pIR) ( > 10% of viable tumour). At data analysis, PFS and OS median follow-up times were longer than 20 months. Results: No statistically significant differences in TCR repertoire in terms of evenness (p = 0,373), diversity (p = 0,691) or convergence (p = 0,054) between pre- and post-neoadjuvant treatment were observed. Similarly, no significant differences were observed in these metrics between pathological response groups. However, a detailed analysis of the clones showed that the percentage of frequent clones (greater than 0.1%) that increase after neoadjuvant therapy does show differences between the different pathological response groups (pIR vs pMR), being elevated in patients who presented responses greater than 90% (p = 0.0385). Regarding the clinical benefit, having this parameter higher than the median (43,90% in this cohort) is associated with a higher PFS (p = 0.0490) and OS (p = 0.078) using KM Log-rank test. Conclusions: Evenness, Diversity and Convergence derived from immune repertoire analysis do not appear to be clinically useful in the context of neoadjuvant chemo-immunotherapy in lung cancer. However, the detailed analysis of the clones seems promising. The increase of the most frequent clones after treatment seems to be associated to different clinical variables such as pathological response and PFS in these patients. Clinical trial information: NCT03081689

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Track

Lung Cancer

Sub Track

Local-Regional Non–Small Cell Lung Cancer

Clinical Trial Registration Number

NCT03081689

Citation

J Clin Oncol 38: 2020 (suppl; abstr 9041)

DOI

10.1200/JCO.2020.38.15_suppl.9041

Abstract #

9041

Poster Bd #

234

Abstract Disclosures