Abstract
Compared to chemotherapy alone, monoclonal antibodies like ipilimumab and nivolumab, with or without chemotherapy, improve the prognosis of patients with non-small cell lung cancer (NSCLC), albeit with a higher incidence of immune-related adverse events (irAEs) than those with immune checkpoint inhibitor (ICI) monotherapy. Therefore, we aimed to investigate if baseline overall tumor burden was associated with the development of Grade ≥ 3 irAEs (severe irAEs) when treated with first-line ipilimumab plus nivolumab with or without chemotherapy.
We retrospectively examined consecutive patients with advanced NSCLC who received nivolumab plus ipilimumab with or without chemotherapy at Hakodate Goryoukaku Hospital between December 2020 and December 2021. Baseline overall tumor burden was measured as the sum of unidimensional diameters of up to five target lesions according to the Response Evaluation Criteria in Solid Tumors, version 1.1. We defined irAEs as ICI therapy-related toxicities according to the Common Terminology Criteria for Adverse Events, version 5.0.
A significant difference in tumor burden was observed between patients with and without severe irAEs (100 mm vs. 67.5 mm, p = 0.001). We evaluated various clinical parameters, including baseline overall tumor burden, before treatment initiation. Of the various parameters, only high tumor burden correlated with severe irAEs, independent of complementary chemotherapy. The multivariate odds ratio of severe irAEs and high tumor burden was 6.62.
Conclusively, baseline overall tumor burden may be a risk factor for severe irAEs in patients treated with first-line combination ICI therapy. Therefore, patients with large tumor burden should be carefully monitored to prevent irAEs.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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The idea of the study was concieved by Toshiyuki Sumi. The statistical analysis plan was developed and conducted by Motoki Sekikawa, Yuta Nagahisa, Keigo Matsuura, Naoki Shijubou, Koki Kamada, Hiroki Watanabe, and Yuichi Yamada. Interpretation of the results was done by Yusuke Tanaka. The original manuscript was drafted by Toshiyuki Sumi. Hirofumi Chiba supervised the conduct of this study. All authors reviewed the manuscript draft and revised it critically for the intellectual content. All authors read and approved the final manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval of the research protocol was granted by the Institutional Ethics Committee of the Hakodate Goryoukaku Hospital (approval no. 2021-057).
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Sumi, T., Sekikawa, M., Nagahisa, Y. et al. Relation of overall tumor burden with severe immune-related adverse events in nivolumab plus ipilimumab treatment for lung cancer. Invest New Drugs 40, 1315–1321 (2022). https://doi.org/10.1007/s10637-022-01305-8
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DOI: https://doi.org/10.1007/s10637-022-01305-8