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Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors
  1. Giovanni Fucà1,
  2. Giulia Galli1,
  3. Marta Poggi1,
  4. Giuseppe Lo Russo1,
  5. Claudia Proto1,
  6. Martina Imbimbo1,
  7. Roberto Ferrara1,
  8. Nicoletta Zilembo1,
  9. Monica Ganzinelli1,
  10. Antonio Sica2,3,
  11. Valter Torri4,
  12. Mario Paolo Colombo5,
  13. Claudio Vernieri1,6,
  14. Andrea Balsari7,
  15. Filippo de Braud1,8,
  16. Marina Chiara Garassino1,
  17. Diego Signorelli1
  1. 1 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
  2. 2 Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale 'Amedeo Avogadro', Novara, Italy
  3. 3 Department of Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Italy
  4. 4 Laboratory of Methodology for Biomedical Research, IRCCS Mario Negri Institute for Pharmacological Research, Milan, Italy
  5. 5 Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
  6. 6 Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy
  7. 7 Dipartimento di Scienze Biomediche per la Salute, University of Milan, Milan, Italy
  8. 8 Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
  1. Correspondence to Dr Marina Chiara Garassino; marina.garassino{at}istitutotumori.mi.it

Abstract

Background Steroids are frequently used in patients with metastatic non-small cell lung cancer (mNSCLC), but they could be detrimental for patients treated with immune checkpoint inhibitors (ICIs). Here, we assessed the association between early use of steroids, clinical outcomes and peripheral immune blood cells modulation in patients with mNSCLC treated with ICIs.

Methods We reviewed patients with mNSCLC treated at our institution between April 2013 and December 2017. Early use of steroids was defined as the use of a daily prednisone-equivalent dose ≥10 mg for at least 1 day within 28 days after ICI initiation. Peripheral immune blood cell counts were retrieved at baseline and at 4 and 6 weeks after ICI initiation.

Results Out of 151 patients included, 35 (23%) made early use of steroids that was associated with poor disease control (OR 0.32, p=0.006), progression-free survival (HR 1.80, p=0.003) and overall survival (HR 2.60, p<0.001). Early use of steroids significantly correlated with higher median absolute neutrophil count, neutrophil to lymphocyte ratio (NLR) and derived NLR, and lower median absolute and relative eosinophil count, both at 4 and 6 weeks after ICI initiation.

Conclusions In patients with mNSCLC treated with ICIs, early use of steroids was associated with worse clinical outcomes and remarkable modulation of peripheral blood immune cells, which could contribute to restraining the activation of antitumour immunity. If confirmed in prospective studies, these findings would highlight the importance of carefully evaluating and, whenever possible, avoiding steroids during early phases of ICI treatment.

  • non-small cell lung cancer
  • immune checkpoint inhibitors
  • steroids

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, any changes made are indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • GF and GG are joint first authors.

  • Contributors Study concept and design: GF, MCG, DS. Data acquisition: GF, GG, MP, GLR, CP, MI, RF, MG. Data analysis: GF, VT. Data interpretation: GF, CV, RF, NZ, MPC, AS, AB, FdB, MCG, DS. Manuscript preparation: GF, GG, CV, AS, MPC, AB, MCG, MG. Manuscript review: GF, GG, GLR, CP, MI, RF, NZ, MG, AS, AB, VT, MPC, DS, MCG, FdB.

  • Funding This research was supported by the Italian Ministry of Health with the research grant 5x1000/2014 (CUP: B43C17000350001) to MCG.

  • Competing interests GLR declares personal fees from Eli Lilly, BMS and AstraZeneca, outside the submitted work. CP declares personal fees from BMS and MSD, outside the submitted work. MCG declares personal fees from MSD, AstraZeneca, Eli Lilly and BMS, outside the submitted work. DS declares personal fees from AstraZeneca, Boehringer Ingelheim and BMS, outside the submitted work.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the local Institutional Review Board (INT 22_15) and conducted according to the ethical principles for medical research involving human subjects adopted in the Declaration of Helsinki. All patients signed a written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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