Clinical and Genomic Characterization of Long-Term Responders Receiving Immune Checkpoint Blockade for Metastatic Non-Small-Cell Lung Cancer.

Objectives: Understand from a real-world cohort the unique clinical and genomic determinants of a durable response to immune checkpoint inhibitors (ICIs).
Materials and Methods: This is a retrospective study of patients with NSCLC who received any ICI-based regimen as first or second line therapy. Long-term responders (LTR) achieved an overall survival (OS) ≥ 3 years from time of treatment start, while nonresponders (NR) were patients who had an OS of 6 to 12 months from time of treatment start. Clinical and demographic covariables were collected from electronic medical records. Fisher's exact test and Mann-Whitney test were used to analyze the association of a long-term response to ICI in relation to clinical and genomic variables. All P-values were considered significant at P-value < .05.
Results: A total of 72 patients were included in this study (LTR n = 37, NR n = 35). There were no significant differences in age, sex, race, and BMI between groups. The presence of liver metastases at the time of ICI initiation and PD-L1 status were not associated with LTR to ICIs. Patients in the LTR were more likely to experience irAEs at 3-,6- and 12-months. KRAS mutant tumors were numerically more common in the LTR group (n = 13 vs. 8).
Conclusion: We observe no strong clinical and biomarkers of a prolonged response to ICIs. Additional large prospective cohort studies are needed to investigate the genomic footprint of long-term responders.
Competing Interests: Disclosure PG has no disclosures. JCM is a consultant for Regeneron, Johnson & Johnson and Doximity. JM receives research funding to the institution from Merck. MH is a consultant for Regeneron and MJH Life Sciences. MZG has no disclosures. DSE has no disclosures. JF receives research funding to the institution from AstraZeneca, Bristol Myers and Pfizer. JF is a consultant for Regeneron, Coherus, AstraZeneca, Bristol Myers, Merck, Takeda and Eli Lilly. PF received research funding to the institution from AstraZeneca, BMS, Corvus, Kyowa, Novartis and Regeneron. PF is a consultant for Amgen, AstraZeneca, BMS, Daiichi, F-Star, G1, Genentech, Janssen, Iteos, Merck, Sanofi, Novartis and Surface. CH is a consultant for Amgen and AstraZeneca. CH receives research funding to the institution form AbbVie, Amgen, AstraZeneca, and BMS. VL is a consultant for Seattle Genetics, Bristol-Myers Squibb, AstraZeneca, Guardant Health, Takeda and Anheart Therapeutics. VL receives funding to the institution from BMS, Merck, Seattle Genetics and AstraZeneca. BL is a consultant for Genentech, Eli Lilly, Astra Zeneca, Pfizer, Daiichi Sankyo, Janssen, Mirati, Amgen, Merck and Sanofi. VA receives research funding to Johns Hopkins University from Astra Zeneca, Personal Genome Diagnostics and Delfi Diagnostics and has received research funding to Johns Hopkins University from Bristol-Myers Squibb in the past 5 years. V.A. is an advisory board member for Neogenomics and V.A. is an inventor on patent applications (63/276,525, 17/779,936, 16/312,152, 16/341,862, 17/047,006, and 17/598,690) submitted by Johns Hopkins University related to cancer genomic analyses, ctDNA therapeutic response monitoring and immunogenomic features of response to immunotherapy that have been licensed to 1 or more entities. Under the terms of these license agreements, the University and inventors are entitled to fees and royalty distributions. JRB is an advisor for Amgen, AstraZeneca, BMS, Genentech/Roche, GlaxoSmithKline, Merck, Sanofi, Regeneron, Janssen and Johnson & Johnson. JRB also receives to the institution research funding from AstraZeneca and BMS. JRB is also part of the Data and Safety monitory board of Janssen. KM receives honoraria from AstraZeneca. KM is a consultant for AstraZeneca, Amgen, Puma Biotechnology, Janssen, Mirati Therapeutics, Mirati Therapeutics and Regeneron. KM receives research funding to the institution from Mirati, BMS, AstraZeneca.
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