Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer
Itroduction. Immune checkpoint inhibitors have become the standard of care for patients with advanced non-small cell lung cancer. However, despite the determination of programmed death-ligand 1 expression in clinical practice, which determines the effectiveness of therapy, up to 80 % of patients wit...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | Russian |
| Published: |
ABV-press
2022-06-01
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| Series: | Успехи молекулярной онкологии |
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| Online Access: | https://umo.abvpress.ru/jour/article/view/441 |
| _version_ | 1826559140891197440 |
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| author | A. A. Musaelyan S. V. Lapin M. A. Urtenova S. V. Odintsova I. V. Chistyakov A. M. Ulitin N. T. Ismanbaev A. L. Akopov S. V. Orlov |
| author_facet | A. A. Musaelyan S. V. Lapin M. A. Urtenova S. V. Odintsova I. V. Chistyakov A. M. Ulitin N. T. Ismanbaev A. L. Akopov S. V. Orlov |
| author_sort | A. A. Musaelyan |
| collection | DOAJ |
| description | Itroduction. Immune checkpoint inhibitors have become the standard of care for patients with advanced non-small cell lung cancer. However, despite the determination of programmed death-ligand 1 expression in clinical practice, which determines the effectiveness of therapy, up to 80 % of patients with non-small cell lung cancer do not respond to treatment.The study objective – investigation of the prognostic role of clinical and immunological markers during immune checkpoint inhibitor monotherapy in ≥2 lines in patients with advanced non-small cell lung cancer.Materials and methods. The study included 45 patients with advanced non-small cell lung cancer receiving programmed cell death 1 / programmed death-ligand 1 inhibitors in monotherapy in 2 and subsequent lines (Group 1), as well as 30 patients with advanced non-small cell lung cancer receiving first-line chemotherapy (Group 2). All patients from 2 groups did not have autoimmune diseases before starting treatment. The determination of autoantibodies, β-2-microglobulin, neopterin, interleukin 6, interleukin 18 and the allelic variant of HLA-DRB1 in patients in the Group 1 was carried out 2 months after the start of therapy, and in the Group 2 – before the start of the next chemotherapy cycle.Results. In Group 1, the presence of EGFR / ALK mutations is an independent predictor of shorter progression-free survival (p = 0.018). Also, in the univariate analysis, neutrophil-lymphocyte ratio <5 before immune checkpoint inhibitors (p = 0.009) and the appearance of immune-related adverse events (p = 0.038) are associated with long-term progressionfree survival. In Group 1, β-2-microglobulin was lower in patients with a response duration of ≥6 months than with a progression <6 months: 1.7 mg / L and 2.9 mg / L, respectively (p <0.0001). Patients receiving immune checkpoint inhibitors with a β-2-microglobulin level ≥2.5 mg / L have a shorter progression-free survival than patients with a marker value <2.5 mg / L: 168 days and the value is not reached, respectively (p = 0.017). In response duration ≥6 months neopterin value was lower than in disease progression: 8.6 nmol / l and 13.4 nmol / L, respectively (p <0,0001). Progression-free survival was lower in patients with neopterin ≥12 nmol / L than patients with neopterin <12 nmol / L: median was 164 days and the value was not reached, respectively (p = 0.0007). Based on the results of multivariate analysis, β-2-microglobulin ≥2.5 mg / L (p = 0.006) and neopterin ≥12 nmol / L (p = 0.027) were independent predictors of shorter progression-free survival. Low levels of interleukin 6 and interleukin 18, as well as antibodies to thyroperoxidase, are associated with a response of ≥6 months. HLA-DRB1*03 was associated with a duration of response of ≥6 months, as well as a longer progression-free survival compared with other allelic variants. The levels of β-2-microglobulin, neopterin, interleukin 6, interleukin 18 were higher in patients in Group 1 than in patients in Group 2 (p <0.0001).Conclusion. Immunological markers can serve as promising prognosis markers in patients with advanced non-small cell lung cancer during immunotherapy. |
| first_indexed | 2024-03-12T18:43:35Z |
| format | Article |
| id | doaj.art-3ad6732d802f458d83f8727e411fce75 |
| institution | Directory Open Access Journal |
| issn | 2313-805X 2413-3787 |
| language | Russian |
| last_indexed | 2025-03-14T08:55:40Z |
| publishDate | 2022-06-01 |
| publisher | ABV-press |
| record_format | Article |
| series | Успехи молекулярной онкологии |
| spelling | doaj.art-3ad6732d802f458d83f8727e411fce752025-03-02T12:45:08ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872022-06-0192798810.17650/2313-805X-2022-9-2-79-88243Immunological markers for predicting the response to immunotherapy in non-small cell lung cancerA. A. Musaelyan0S. V. Lapin1M. A. Urtenova2S. V. Odintsova3I. V. Chistyakov4A. M. Ulitin5N. T. Ismanbaev6A. L. Akopov7S. V. Orlov8I.P. Pavlov First Saint-Petersburg State Medical University; Research Institute of Medical PrimatologyI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical UniversityI.P. Pavlov First Saint-Petersburg State Medical University; Research Institute of Medical PrimatologyItroduction. Immune checkpoint inhibitors have become the standard of care for patients with advanced non-small cell lung cancer. However, despite the determination of programmed death-ligand 1 expression in clinical practice, which determines the effectiveness of therapy, up to 80 % of patients with non-small cell lung cancer do not respond to treatment.The study objective – investigation of the prognostic role of clinical and immunological markers during immune checkpoint inhibitor monotherapy in ≥2 lines in patients with advanced non-small cell lung cancer.Materials and methods. The study included 45 patients with advanced non-small cell lung cancer receiving programmed cell death 1 / programmed death-ligand 1 inhibitors in monotherapy in 2 and subsequent lines (Group 1), as well as 30 patients with advanced non-small cell lung cancer receiving first-line chemotherapy (Group 2). All patients from 2 groups did not have autoimmune diseases before starting treatment. The determination of autoantibodies, β-2-microglobulin, neopterin, interleukin 6, interleukin 18 and the allelic variant of HLA-DRB1 in patients in the Group 1 was carried out 2 months after the start of therapy, and in the Group 2 – before the start of the next chemotherapy cycle.Results. In Group 1, the presence of EGFR / ALK mutations is an independent predictor of shorter progression-free survival (p = 0.018). Also, in the univariate analysis, neutrophil-lymphocyte ratio <5 before immune checkpoint inhibitors (p = 0.009) and the appearance of immune-related adverse events (p = 0.038) are associated with long-term progressionfree survival. In Group 1, β-2-microglobulin was lower in patients with a response duration of ≥6 months than with a progression <6 months: 1.7 mg / L and 2.9 mg / L, respectively (p <0.0001). Patients receiving immune checkpoint inhibitors with a β-2-microglobulin level ≥2.5 mg / L have a shorter progression-free survival than patients with a marker value <2.5 mg / L: 168 days and the value is not reached, respectively (p = 0.017). In response duration ≥6 months neopterin value was lower than in disease progression: 8.6 nmol / l and 13.4 nmol / L, respectively (p <0,0001). Progression-free survival was lower in patients with neopterin ≥12 nmol / L than patients with neopterin <12 nmol / L: median was 164 days and the value was not reached, respectively (p = 0.0007). Based on the results of multivariate analysis, β-2-microglobulin ≥2.5 mg / L (p = 0.006) and neopterin ≥12 nmol / L (p = 0.027) were independent predictors of shorter progression-free survival. Low levels of interleukin 6 and interleukin 18, as well as antibodies to thyroperoxidase, are associated with a response of ≥6 months. HLA-DRB1*03 was associated with a duration of response of ≥6 months, as well as a longer progression-free survival compared with other allelic variants. The levels of β-2-microglobulin, neopterin, interleukin 6, interleukin 18 were higher in patients in Group 1 than in patients in Group 2 (p <0.0001).Conclusion. Immunological markers can serve as promising prognosis markers in patients with advanced non-small cell lung cancer during immunotherapy.https://umo.abvpress.ru/jour/article/view/441predictive markersimmune-related adverse eventsnon-small cell lung cancerimmunotherapy |
| spellingShingle | A. A. Musaelyan S. V. Lapin M. A. Urtenova S. V. Odintsova I. V. Chistyakov A. M. Ulitin N. T. Ismanbaev A. L. Akopov S. V. Orlov Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer Успехи молекулярной онкологии predictive markers immune-related adverse events non-small cell lung cancer immunotherapy |
| title | Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer |
| title_full | Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer |
| title_fullStr | Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer |
| title_full_unstemmed | Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer |
| title_short | Immunological markers for predicting the response to immunotherapy in non-small cell lung cancer |
| title_sort | immunological markers for predicting the response to immunotherapy in non small cell lung cancer |
| topic | predictive markers immune-related adverse events non-small cell lung cancer immunotherapy |
| url | https://umo.abvpress.ru/jour/article/view/441 |
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