419P - Predictors and outcomes of non-small cell lung carcinoma (NSCLC) patients following severe immune checkpoint inhibitor (ICI) toxicity: A real-world UK multi-centre study

Background

We investigated outcomes and their predictors in NSCLC patients (pts) treated with an ICI following a severe immune-related adverse event (irAE).

Methods

We included all NSCLC pts receiving ≥1 ICI cycle and corticosteroids for CTCAE ≥ Grade 3 irAEs between 2017–2023 at Oxford University, Guy’s and St. Thomas’ and University College London Hospitals. Progression Free Survival (PFS) and Overall Survival (OS) after 1st irAE and predictors of clinical benefit were evaluated. Kaplan-Meier and multivariate Cox regression models were used.

Results

We screened 1658 NSCLC pts and identified 80 eligible. Median age was 69 y, male=51%. Most pts had metastatic (N=50, 63%) vs localised (37%) NSCLC. Genomic alterations occurred in KRAS (N=29, 36%) and EGFR (N=4, 5%). Most pts developed a single ≥ Grade 3 irAE on 1^st line ICI (N=71, 89%); frequently colitis (N=26, 33%), pneumonitis (N=14, 18%), hepatitis (N=13, 16%) and acute kidney injury (N=7, 9%). Overall, 14 (18%) pts developed 2^nd irAEs, 7 after rechallenge. In the complete cohort, median OS after 1^st irAE was 15.8 months (95% CI, 12.4–26.9). Lower neutrophil-to-lymphocyte ratio (NLR) (≤6.5 vs >6.5), pts receiving >4 cycles of ICI prior to 1^st irAE or median duration of ICI of >2.8 months prior to 1^st irAE were associated with improved OS (P < 0.05), the latter two with PFS (P < 0.05). Age, gender, stage, KRAS mutations, PD-L1 were not associated with PFS or OS. Pts with pneumonitis as 1^st irAE had the worst PFS and OS (P < 0.05). Pts receiving a median starting prednisolone dose of ≤60 mg for 1^st irAE had an improved OS (P=0.04). Number of irAEs, additional immunosuppressive agents (14% of pts), resumption vs discontinuing all systemic treatment were not associated with PFS or OS.

Conclusions

In this real-world analysis of pts experiencing ≥ Grade 3 irAEs managed with steroids, promising outcomes were observed in pts with lower baseline NLR and those receiving ICIs for longer periods. Pneumonitis was the irAE associated with poorest prognosis. A lower than 60 mg prednisolone dose for the treatment of irAE correlated with improved OS but continuing vs terminating ICI was not associated with OS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J. Spicer: Financial Interests, Institutional, Advisory Board, Compensation to my employer for time providing advice: AstraZeneca, BMS, GSK, RS Oncology; Financial Interests, Personal, Member of Board of Directors: APOBEC Discovery; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Personal, Stocks/Shares: Avacta; Financial Interests, Institutional, Invited Speaker, Reimbursement for treatment of patients in trial: Achilles, Roche, Starpharma, BergenBio, BMS, IO Biotech, MSD, RS Oncology, Gilead, Iovance, Nucana; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, National strategy board: Experimental Cancer Medicine Centres; Non-Financial Interests, Personal, Member of Board of Directors, Steering Committee: British Thoracic Oncology Group; Non-Financial Interests, Personal, Advisory Role, Advice on licensing decisions for MHRA: CHM Expert Advisory Group on Oncology & Haematology; Non-Financial Interests, Personal, Advisory Role, Advice on regulatory approvals: CHM Highly Personalised Medicines Expert Working Group. T. Ahmad: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Meeting attendance support: Takeda. M.D. Forster: Financial Interests, Personal, Advisory Board: Bayer, Merck, MSD, Roche, Takeda, ultrahuman, Transgene, Immunotep, Amgen, BMS, EQRx, GSK, Janssen, Oxford VacMedix, PharmaMar, Regeneron, Syncorp; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Institutional, Invited Speaker: Roche, Oxford VaxMedix, Apollomics, takeda, Ellipsis, Moderna, Exsciencia, ALXOncology, GenMab, Janssen; Financial Interests, Personal and Institutional, Invited Speaker, Presented data at ESMO-IO 2022: Achilles; Financial Interests, Institutional, Invited Speaker, Presented Data at SITC 2023: Immutep; Non-Financial Interests, Personal, Advisory Role, Chair of Scientific Advisory Group: Ruth Strauss Foundation. M. Jamal-Hanjani: Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Oslo Cancer Cluster, Astex Pharmaceutical; Financial Interests, Personal, Invited Speaker, Speaker honorarium: Pfizer, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Cancer cachexia research advisory board: Pfizer; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board and Steering Committee member: Achilles Therapeutics; Other, Personal, Other, I am named as co-inventor on patent PCT/US2017/028013 relating to methods for lung cancer detection.: Patent. C. Swanton: Financial Interests, Personal, Invited Speaker, Activity took place in 2016.: Pfizer, Celgene; Financial Interests, Personal, Invited Speaker, October 26^th 2020: Novartis; Financial Interests, Personal, Invited Speaker: Roche/Ventana, BMS, AstraZeneca, MSD, Illumina, GSK; Financial Interests, Personal, Advisory Board, Ad Board - November 12th, 2020: Amgen; Financial Interests, Personal, Advisory Board, Current - since 2018: Genentech; Financial Interests, Personal, Advisory Board: Sarah Canon Research Institute; Financial Interests, Personal, Advisory Board, Joined October 2020. Also have stock options: Bicycle Therapeutics; Financial Interests, Personal, Other, Consultancy: Medicxi; Financial Interests, Personal, Advisory Board, Member of the Science Advisory Board. Also had stock options until June 2021: GRAIL; Financial Interests, Personal, Other, Consultancy agreement: Roche Innovation Centre Shanghai; Financial Interests, Personal, Advisory Board, 29 November - 1 December 2022: Novartis; Financial Interests, Personal, Invited Speaker, Oncology Collective - 2^nd Nov - 4 Nov 2022 - Atlanta, USA: Roche; Financial Interests, Personal, Advisory Board, ctDNA advisory Board - 24^th March 2023: AstraZeneca; Financial Interests, Personal, Invited Speaker, Pfizer Oncology ‘Leading the revolution for the future: Pfizer; Financial Interests, Personal, Advisory Board, Scientific Advisory Board and Stock options from September 2023.: Relay Therapeutics; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board.: SAGA Diagnostics; Financial Interests, Personal, Full or part-time Employment, Chief Clinician since October 2017: Cancer Research UK; Financial Interests, Personal, Ownership Interest, Co-Founder of Achilles Therapeutics. Also, have stock options in this company.: Achilles Therapeutics; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: GRAIL, Apogen Biotechnologies; Financial Interests, Personal, Stocks/Shares: Epic Biosciences, Bicycle Therapeutics; Financial Interests, Personal, Stocks/Shares, Stock options: Relay Therapeutics; Financial Interests, Institutional, Research Grant, Funded RUBICON grant - October 2018 - April 2021.: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Collaboration in minimal residual disease sequencing technologies.: Archer Dx Inc; Financial Interests, Institutional, Research Grant: Pfizer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker, Chief Investigator for the MeRmaiD 1and 2 clinical trials and chair of the steering committee.: AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant from Oct 2019 - July 2023 - Genetics of CIN and SCNAs for Targeted Discovery (SCEPTRE): Ono Pharmaceutical; Financial Interests, Institutional, Research Grant, Research Grants from 2015: Roche; Financial Interests, Personal, Other, Co-chief investigator: NHS-Galleri Clinical Trial; Financial Interests, Institutional, Research Grant, from October 2022: Personalis; Non-Financial Interests, Personal, Principal Investigator, Chief Investigator for MeRmaiD 1and 2 clinical trials: AstraZeneca; Non-Financial Interests, Personal, Member of Board of Directors, From 2019–2022: AACR; Non-Financial Interests, Personal, Other, Board of Directors: AACR; Non-Financial Interests, Personal, Advisory Role, EACR Advisory Council member: EACR. S.M. Lee: Other, Personal and Institutional, Other, S.M.L. is partially supported by the UCL/UCLH NIHR Biomedical Centre.: UCL/UCLH NIHR Biomedical Centre. D. Papadatos-Pastos: Financial Interests, Personal, Other, Travel support outside of submitted work.: Merck; Financial Interests, Personal, Other: Takeda, MSD, AstraZeneca, Pfizer, Amgen. All other authors have declared no conflicts of interest.