Synapse - Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non

Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non–small cell lung cancer Journal Article

Authors:	Thummalapalli, R.; Ricciuti, B.; Bandlamudi, C.; Muldoon, D.; Rizvi, H.; Elkrief, A.; Luo, J.; Alessi, J. V.; Pecci, F.; Lamberti, G.; Di Federico, A.; Hong, L.; Zhang, J.; Heymach, J. V.; Gibbons, D. L.; Plodkowski, A. J.; Ravichandran, V.; Donoghue, M. T. A.; Vanderbilt, C.; Ladanyi, M.; Rudin, C. M.; Kris, M. G.; Riely, G. J.; Chaft, J. E.; Hellmann, M. D.; Vokes, N. I.; Awad, M. M.; Schoenfeld, A. J.
Article Title:	Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non–small cell lung cancer
Abstract:	Purpose: We sought to identify features of patients with advanced non–small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR). Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), next-generation sequencing (NGS), and whole-exome sequencing (WES) data were analyzed to identify characteristics enriched in patients achieving LTR compared with STR and non-LTR. Results: Among 3,118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival (OS) of 81% and 18% among LTR and STR patients, respectively. High TMB (≥50th percentile) enriched for LTR compared with STR (P = 0.001) and non-LTR (P < 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared with non-LTR (P < 0.001), PD-L1 ≥ 50% did not enrich for LTR compared with STR (P = 0.181). Nonsquamous histology (P = 0.040) and increasing depth of response [median best overall response (BOR) -65% vs. -46%, P < 0.001] also associated with LTR compared with STR; no individual genomic alterations were uniquely enriched among LTR patients. Conclusions: Among patients with advanced NSCLC treated with ICIs, distinct features including high TMB, nonsquamous histology, and depth of radiographic improvement distinguish patients poised to achieve LTR compared with initial response followed by progression, whereas high PD-L1 does not. © 2023 The Authors; Published by the American Association for Cancer Research.
Keywords:	retrospective studies; genetics; clinical trial; carcinoma, non-small-cell lung; lung neoplasms; pathology; retrospective study; tumor marker; lung tumor; multicenter study; programmed death 1 ligand 1; non small cell lung cancer; immune checkpoint inhibitor; humans; human; immune checkpoint inhibitors; biomarkers, tumor; immunological antineoplastic agent; antineoplastic agents, immunological; b7-h1 antigen
Journal Title:	Clinical Cancer Research
Volume:	29
Issue:	21
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2023-11-01
Start Page:	4408
End Page:	4418
Language:	English
DOI:	10.1158/1078-0432.Ccr-23-1207
PUBMED:	37432985
PROVIDER:	scopus
PMCID:	PMC10618656
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85175741359&doi=10.1158%2f1078-0432.CCR-23-1207&partnerID=40&md5=801b26e7e5e6d2a08eabe0f663c7a0a6
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Adam Schoenfeld -- Source: Scopus