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Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation

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Abstract

Background

The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood.

Methods

The Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported. The primary end points were median progression-free survival, overall survival, objective response rate, risk of progression of disease and risk of death. The correlation of clinic pathological features with early severe irAEs represented the secondary end point.

Results

Median PFS was 9.3 and 8.4 months, median OS was 12.0 months and 14.2 months at a median follow-up of 18.1 and 22.6 months in the LTD cohort and in the control cohort, respectively. The ORR was 40% (95% CI 17.2–78.8) in the LTD cohort and 32.7% (95% CI 27.8–38.2) in the control cohort. The risk of disease progression was higher in the LTD cohort (HR 2.52 [95% 1.10–5.78], P = .0288).

Conclusions

We found no survival benefit in LTD cohort compared to the control cohort. However, early and severe irAEs might underly an immune anti-tumor activation. We identified a significant association with first-line immune checkpoints inhibitors treatment and good PS. Further studies on risk prediction and management of serious and early irAEs in NSCLC patients are needed.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CTCAE:

Common Toxicity Criteria for Adverse Events

CI:

Confidence intervals (CI)

ECOG-PS:

Eastern Cooperative Oncology Group-Performance Status

HR:

Hazard ratios

ICIs:

Immune checkpoints inhibitors

irAEs:

Immune-related adverse events

LTD cohort:

Leading to treatment discontinuation cohort

NSCLC:

Non-small cell lung cancer

ORR:

Objective response rate

OR:

Odds radios

OS:

Overall survival

PD-1:

Programmed death-1

PD-L1:

Programmed death-ligand 1

PFS:

Progression-free survival

References

  1. Ackermann CJ, Adderley H, Ortega-Franco A, Khan A, Reck M, Califano R (2020) First-line immune checkpoint inhibition for advanced non-small-cell lung cancer: state of the art and future directions. Drugs 80(17):1783–1797. https://doi.org/10.1007/s40265-020-01409-6

    Article  PubMed  Google Scholar 

  2. Berghmans T, Dingemans AM, Hendriks LEL, Cadranel J (2020) Immunotherapy for nonsmall cell lung cancer: a new therapeutic algorithm. Eur Respir J 55(2):1901907. https://doi.org/10.1183/13993003.01907-2019

    Article  PubMed  Google Scholar 

  3. Pabani A, Butts CA (2018) Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer. Curr Oncol 25(Suppl 1):S94–S102. https://doi.org/10.3747/co.25.3750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB (2017) Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol 8:49. https://doi.org/10.3389/fphar.2017.00049 [published correction appears in Front Pharmacol 2017 8:311. https://doi.org/10.3389/fphar.2017.00311]

  5. Baxi S, Yang A, Gennarelli RL et al (2018) Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ 360:k793. https://doi.org/10.1136/bmj.k793

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ramos-Casals M, Brahmer JR, Callahan MK et al (2020) Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers 6(1):38. https://doi.org/10.1038/s41572-020-0160-6

    Article  PubMed  Google Scholar 

  7. Martins F, Sofiya L, Sykiotis GP et al (2019) Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol 16(9):563–580. https://doi.org/10.1038/s41571-019-0218-0

    Article  CAS  PubMed  Google Scholar 

  8. Haanen JBAG, Carbonnel F, Robert C et al (2018) Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29(Suppl 4):iv264–iv266. https://doi.org/10.1093/annonc/mdy162

    Article  CAS  PubMed  Google Scholar 

  9. Postow MA, Sidlow R, Hellmann MD (2018) Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 378(2):158–168. https://doi.org/10.1056/NEJMra1703481

    Article  CAS  PubMed  Google Scholar 

  10. Das S, Johnson DB (2019) Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer 7(1):306. https://doi.org/10.1186/s40425-019-0805-8

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhou X, Yao Z, Yang H, Liang N, Zhang X, Zhang F (2020) Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis. BMC Med 18(1):87. https://doi.org/10.1186/s12916-020-01549-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rogado J, Sánchez-Torres JM, Romero-Laorden N et al (2019) Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients. Eur J Cancer 109:21–27. https://doi.org/10.1016/j.ejca.2018.10.014

    Article  CAS  PubMed  Google Scholar 

  13. Eggermont AMM, Kicinski M, Blank CU et al (2020) Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive pembrolizumab or placebo: a secondary analysis of a randomized clinical trial. JAMA Oncol 6(4):519–527. https://doi.org/10.1001/jamaoncol.2019.5570

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cortellini A, Bersanelli M, Buti S et al (2019) A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J Immunother Cancer 7(1):57. https://doi.org/10.1186/s40425-019-0527-y

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cortellini A, Bersanelli M, Santini D et al (2020) Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: a multicentre analysis of immune-related adverse events. Eur J Cancer 128:17–26. https://doi.org/10.1016/j.ejca.2019.12.031

    Article  CAS  PubMed  Google Scholar 

  16. Cortellini A, Buti S, Bersanelli M et al (2019) Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study. Oncoimmunology 9(1):1710389. https://doi.org/10.1080/2162402X.2019.1710389

    Article  Google Scholar 

  17. Cortellini A, Vitale MG, De Galitiis F et al (2019) Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice. J Transl Med 17(1):376. https://doi.org/10.1186/s12967-019-02132-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cortellini A, Buti S, Santini D et al (2019) Clinical outcomes of patients with advanced cancer and pre-existing autoimmune diseases treated with anti-programmed death-1 immunotherapy: a real-world transverse study. Oncologist 24(6):e327–e337. https://doi.org/10.1634/theoncologist.2018-0618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cortellini A, Chiari R, Ricciuti B et al (2019) Correlations between the immune-related adverse events spectrum and efficacy of anti-PD1 immunotherapy in NSCLC patients. Clin Lung Cancer 20(4):237-247.e1. https://doi.org/10.1016/j.cllc.2019.02.006

    Article  CAS  PubMed  Google Scholar 

  20. Cortellini A, Tucci M, Adamo V et al (2020) Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice. J Immunother Cancer 8(2):e001361. https://doi.org/10.1136/jitc-2020-001361

    Article  PubMed  PubMed Central  Google Scholar 

  21. Buti S, Bersanelli M, Perrone F et al (2021) Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index. Eur J Cancer 142:18–28. https://doi.org/10.1016/j.ejca.2020.09.033

    Article  CAS  PubMed  Google Scholar 

  22. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  Google Scholar 

  23. Gridelli C, Balducci L, Ciardiello F et al (2015) Treatment of elderly patients with non-small-cell lung cancer: results of an international expert panel meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer 16(5):325–333. https://doi.org/10.1016/j.cllc.2015.02.006

    Article  PubMed  Google Scholar 

  24. Austin PC (2011) Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 10(2):150–161. https://doi.org/10.1002/pst.433

    Article  PubMed  Google Scholar 

  25. Sato K, Akamatsu H, Murakami E et al (2018) Correlation between immune-related adverse events and efficacy in Non-Small Cell Lung Cancer treated with nivolumab. Lung Cancer 115:71–74. https://doi.org/10.1016/j.lungcan.2017.11.019 [published correction appears in Lung Cancer 2018 126:230–231. https://doi.org/10.1016/j.lungcan.2018.11.007]

  26. Akamatsu H, Murakami E, Oyanagi J et al (2020) Immune-related adverse events by immune checkpoint inhibitors significantly predict durable efficacy even in responders with advanced Non-Small Cell Lung Cancer. Oncologist 25(4):e679–e683. https://doi.org/10.1634/theoncologist.2019-0299

    Article  CAS  PubMed  Google Scholar 

  27. Grangeon M, Tomasini P, Chaleat S et al (2019) Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in Non-Small-Cell Lung Cancer. Clin Lung Cancer 20(3):201–207. https://doi.org/10.1016/j.cllc.2018.10.002

    Article  CAS  PubMed  Google Scholar 

  28. Ricciuti B, Genova C, De Giglio A et al (2019) Impact of immune-related adverse events on survival in patients with advanced Non-Small Cell Lung Cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. J Cancer Res Clin Oncol 145(2):479–485. https://doi.org/10.1007/s00432-018-2805-3

    Article  CAS  PubMed  Google Scholar 

  29. Cortellini A, Friedlaender A, Banna GL et al (2020) Immune-related adverse events of pembrolizumab in a large real-world cohort of patients with NSCLC with a PD-L1 expression ≥ 50% and their relationship with clinical outcomes. Clin Lung Cancer 21(6):498-508.e2. https://doi.org/10.1016/j.cllc.2020.06.010

    Article  CAS  PubMed  Google Scholar 

  30. Berner F, Bomze D, Diem S et al (2019) Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in Non-Small Cell Lung Cancer. JAMA Oncol 5(7):1043–1047. https://doi.org/10.1001/jamaoncol.2019.0402 [published correction appears in JAMA Oncol 2019 5(7):1070. https://doi.org/10.1001/jamaoncol.2019.2137]

  31. Weinmann SC, Pisetsky DS (2019) Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors. Rheumatology (Oxford) 58(Suppl 7):vii59–vii67. https://doi.org/10.1093/rheumatology/kez308

    Article  CAS  Google Scholar 

  32. Teraoka S, Fujimoto D, Morimoto T et al (2017) Early immune-related adverse events and association with outcome in advanced Non-Small Cell Lung Cancer patients treated with nivolumab: a prospective cohort study. J Thorac Oncol 12(12):1798–1805. https://doi.org/10.1016/j.jtho.2017.08.022

    Article  PubMed  Google Scholar 

  33. Hosoya K, Fujimoto D, Morimoto T et al (2020) Association between early immune-related adverse events and clinical outcomes in patients with Non-Small Cell Lung Cancer treated with immune checkpoint inhibitors. Clin Lung Cancer 21(4):e315–e328. https://doi.org/10.1016/j.cllc.2020.01.003

    Article  CAS  PubMed  Google Scholar 

  34. Wang Y, Zhou S, Yang F et al (2019) Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis. JAMA Oncol 5(7):1008–1019. https://doi.org/10.1001/jamaoncol.2019.0393

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fukihara J, Sakamoto K, Koyama J et al (2019) Prognostic impact and risk factors of immune-related pneumonitis in patients with Non-Small-Cell Lung Cancer who received programmed death 1 inhibitors. Clin Lung Cancer 20(6):442-450.e4. https://doi.org/10.1016/j.cllc.2019.07.006

    Article  CAS  PubMed  Google Scholar 

  36. Jia XH, Geng LY, Jiang PP et al (2020) The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors. J Exp Clin Cancer Res 39(1):284. https://doi.org/10.1186/s13046-020-01749-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lim SY, Lee JH, Gide TN et al (2019) Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy. Clin Cancer Res 25(5):1557–1563. https://doi.org/10.1158/1078-0432.CCR-18-2795

    Article  CAS  PubMed  Google Scholar 

  38. Fujimura T, Sato Y, Tanita K et al (2018) Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study. Oncotarget 9(21):15542–15551. https://doi.org/10.18632/oncotarget.24509

    Article  PubMed  PubMed Central  Google Scholar 

  39. Jing Y, Liu J, Ye Y et al (2020) Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy. Nat Commun 11(1):4946. https://doi.org/10.1038/s41467-020-18742-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Colen RR, Fujii T, Bilen MA et al (2018) Radiomics to predict immunotherapy-induced pneumonitis: proof of concept. Invest New Drugs 36(4):601–607. https://doi.org/10.1007/s10637-017-0524-2

    Article  CAS  PubMed  Google Scholar 

  41. Sakata Y, Kawamura K, Ichikado K et al (2019) The association between tumor burden and severe immune-related adverse events in Non-Small Cell Lung Cancer patients responding to immune-checkpoint inhibitor treatment. Lung Cancer 130:159–161. https://doi.org/10.1016/j.lungcan.2019.02.011

    Article  PubMed  Google Scholar 

  42. Suazo-Zepeda E, Bokern M, Vinke PC, Hiltermann TJN, de Bock GH, Sidorenkov G (2021) Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis. Cancer Immunol Immunother. https://doi.org/10.1007/s00262-021-02996-3

    Article  PubMed  PubMed Central  Google Scholar 

  43. Santini FC, Rizvi H, Plodkowski AJ et al (2018) Safety and efficacy of re-treating with immunotherapy after immune-related adverse events in patients with NSCLC. Cancer Immunol Res 6(9):1093–1099. https://doi.org/10.1158/2326-6066.CIR-17-0755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kashiwabara K, Fujii S, Tsumura S, Sakamoto K (2020) Timing of resumption of immune checkpoint inhibitor therapy after successful control of immune-related adverse events in seven advanced Non-Small Cell Lung Cancer patients. Anticancer Drugs 31(8):872–875. https://doi.org/10.1097/CAD.0000000000000957

    Article  CAS  PubMed  Google Scholar 

  45. Fujita K, Uchida N, Kanai O, Okamura M, Nakatani K, Mio T (2018) Retreatment with pembrolizumab in advanced Non-Small Cell Lung Cancer patients previously treated with nivolumab: emerging reports of 12 cases. Cancer Chemother Pharmacol 81(6):1105–1109. https://doi.org/10.1007/s00280-018-3585-9

    Article  CAS  PubMed  Google Scholar 

  46. Mouri A, Kaira K, Yamaguchi O et al (2019) Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer. Cancer Chemother Pharmacol 84(4):873–880. https://doi.org/10.1007/s00280-019-03926-y

    Article  CAS  PubMed  Google Scholar 

  47. Fujita K, Uchida N, Yamamoto Y et al (2019) Retreatment with anti-PD-L1 antibody in advanced Non-Small Cell Lung Cancer previously treated with anti-PD-1 antibodies. Anticancer Res 39(7):3917–3921. https://doi.org/10.21873/anticanres.13543

    Article  CAS  PubMed  Google Scholar 

  48. Haanen J, Ernstoff M, Wang Y et al (2020) Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy. J Immunother Cancer 8(1):e000604. https://doi.org/10.1136/jitc-2020-000604

    Article  PubMed  PubMed Central  Google Scholar 

  49. Abou Alaiwi S, Xie W, Nassar AH et al (2020) Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma. J Immunother Cancer 8(1):e000144. https://doi.org/10.1136/jitc-2019-000144

    Article  PubMed  PubMed Central  Google Scholar 

  50. Motzer RJ, Rini BI, McDermott DF et al (2019) Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol 20(10):1370–1385. https://doi.org/10.1016/S1470-2045(19)30413-9 [published correction appears in Lancet Oncol 2019 20(10):e559. https://doi.org/10.1016/S1470-2045(19)30542-X] [published correction appears in Lancet Oncol 2020 21(6):e304. https://doi.org/10.1016/S1470-2045(20)30268-0] [published correction appears in Lancet Oncol 2020 21(11):e518. https://doi.org/10.1016/S1470-2045(20)30598-2]

  51. Komiya K, Nakamura T, Abe T et al (2019) Discontinuation due to immune-related adverse events is a possible predictive factor for immune checkpoint inhibitors in patients with Non-Small Cell Lung Cancer. Thorac Cancer 10(9):1798–1804. https://doi.org/10.1111/1759-7714.13149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Naqash AR, Ricciuti B, Owen DH et al (2020) Outcomes associated with immune-related adverse events in metastatic Non-Small Cell Lung Cancer treated with nivolumab: a pooled exploratory analysis from a global cohort. Cancer Immunol Immunother 69(7):1177–1187. https://doi.org/10.1007/s00262-020-02536-5 [published correction appears in Cancer Immunol Immunother 2020 69(7):1189. https://doi.org/10.1007/s00262-020-02582-z]

  53. Betof Warner A, Palmer JS, Shoushtari AN et al (2020) Long-term outcomes and responses to retreatment in patients with melanoma treated with PD-1 blockade. J Clin Oncol 38(15):1655–1663. https://doi.org/10.1200/JCO.19.01464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pedicord VA, Montalvo W, Leiner IM, Allison JP (2011) Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance. Proc Natl Acad Sci USA 108(1):266–271. https://doi.org/10.1073/pnas.1016791108

    Article  PubMed  Google Scholar 

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Acknowledgements

The present manuscript is not under consideration elsewhere and it has not been published in any form or language. Its submission was approved by all the authors.

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Author notes

  1. Marco Russano and Alessio Cortellini have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128, Rome, Italy

    Marco Russano, Fabrizio Citarella, Francesco Pantano, Bruno Vincenzi, Giuseppe Tonini & Daniele Santini

  2. Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

    Alessio Cortellini, Corrado Ficorella & Giampiero Porzio

  3. Medical Oncology, St. Andrea Hospital, Rome, Italy

    Raffaele Giusti, Marco Filetti & Marta Piras

  4. Medical Oncology, A.O. Papardo and Department of Human Pathology, University of Messina, Messina, Italy

    Alessandro Russo & Vincenzo Adamo

  5. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy

    Federica Zoratto & Enzo Veltri

  6. Medical Oncology, Fermo Area Vasta 4, Fermo, Italy

    Francesca Rastelli & Federica Pergolesi

  7. Medical Oncology (B), Policlinico Umberto I, “Sapienza” University of Rome, Rome, Italy

    Alain Gelibter & Mario Alberto Occhipinti

  8. Medical Oncology, Ospedali Riuniti Padova Sud “Madre Teresa Di Calcutta”, Monselice, Italy

    Rita Chiari & Linda Nicolardi

  9. Medical Oncology, ASST-Sette Laghi, Varese, Italy

    Olga Nigro & Alessandro Tuzi

  10. Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy

    Michele De Tursi, Pietro Di Marino & Clara Natoli

  11. Medical and Translational Oncology Unit, Department of Oncology, Azienda Ospedaliera Santa Maria, 05100, Terni, Italy

    Sergio Bracarda & Serena Macrini

  12. Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, 37024, Negrar, Verona, Italy

    Stefania Gori & Alessandro Inno

  13. Medical Oncology Unit, IRCCS Foundation Ca’ Granda Maggiore Hospital Policlinic, Milan, Italy

    Francesco Grossi, Michele Ghidini & Erika Rijavec

  14. Department of Medicine and Surgery, University of Parma, Parma, Italy

    Melissa Bersanelli, Sebastiano Buti & Marcello Tiseo

  15. Medical Oncology Unit, University Hospital of Parma, Parma, Italy

    Melissa Bersanelli, Sebastiano Buti & Marcello Tiseo

  16. Department of Oncology, San Bortolo General Hospital, Vicenza, Italy

    Lorenzo Calvetti, Giuseppe Aprile & Francesca Simionato

  17. IRCCS Regina Elena National Cancer Institute, Rome, Italy

    Vincenzo Di Noia

  18. Department of Medical Oncology, University Hospital of Cagliari, Cagliari, Italy

    Mario Scartozzi & Eleonora Lai

  19. Department of Oncology, Medical Oncology Unit, Ordine Mauriziano Hospital, University of Turin, Turin, Italy

    Massimo Di Maio & Marco Audisio

  20. Medical Oncology, ASST-Spedali Civili, University of Brescia, Brescia, Italy

    Paolo Bossi & Salvatore Intagliata

  21. Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Alfredo Falcone & Riccardo Marconcini

  22. Department of Pharmacy, G. d’Annunzio” University of Chieti-Pescara, Via Dei Vestini 31, 66100, Chieti, Italy

    Davide Brocco

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  1. Marco Russano
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Contributions

All authors were involved in the writing of this manuscript and read and approved the final manuscript.

Corresponding author

Correspondence to Fabrizio Citarella.

Ethics declarations

Conflict of interest

Alessio Cortellini received speaker fees and grant consultancies from Roche, MSD, BMS, AstraZeneca, Novartis, Astellas. Marco Russano received honoraria for consultancy and scientific talks from Roche, BMS, MSD, Boehringer Ingelheim, AstraZeneca. Daniele Santini received speaker fees and grant consultancies from Janssen, Astellas, BMS, MSD, Pfizer, Boeringher Ingelheim, Roche, Eisai, Incyte, Novartis. Marcello Tiseo received speakers’ and consultants’ fee from AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre. Marcello Tiseo received institutional research grants from AstraZeneca, Boehringer Ingelheim. Sebastiano Buti received honoraria as a speaker at scientific events and advisory role by Bristol-Myers Squibb (BMS), Pfizer; MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca, Pierre Fabre and Novartis.

Ethics approval

The study was approved by the respective local ethical committees on human experimentation of each institution, after previous approval by the coordinating center. The procedures followed were in accordance with the precepts of Good Clinical Practice and the declaration of Helsinki. IRB reference for the control cohort: University of L’Aquila, Internal Review Board protocol number 32865, approved on July 24th, 2018. IRB reference for the LTD cohort: Campus Bio-medico University of Rome, protocol number 37/19 OSS approved on July 24th, 2019.

Consent to participate

All patients alive at the time of data collection provided an informed consent for the present retrospective analysis.

Consent for publication

The authors affirm that human research participants provided informed consent for publication of the images.

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Russano, M., Cortellini, A., Giusti, R. et al. Clinical outcomes of NSCLC patients experiencing early immune-related adverse events to PD-1/PD-L1 checkpoint inhibitors leading to treatment discontinuation. Cancer Immunol Immunother 71, 865–874 (2022). https://doi.org/10.1007/s00262-021-03045-9

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