Immunohistochemical factors of prognosis of immunotherapy for metastatic melanoma: А prospective and retrospective study
- 作者: Oganesyan L.1,2, Zavalishina L.1, Ognerubov N.3, Kostalanova I.4,5, Orlov A.4,5,6, Poddubnaya I.1
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隶属关系:
- Russian Medical Academy of Continuous Professional Education
- Loginov Moscow Clinical Scientific Center
- Penza Institute for Further Training of Physicians – branch of the Russian Medical Academy of Continuous Professional Education
- Samara State Medical University
- Samara Regional Clinical Oncology Dispensary
- Ministry of Healthcare of Samara Region
- 期: 卷 26, 编号 2 (2024)
- 页面: 190-196
- 栏目: Articles
- URL: https://journals.rcsi.science/1815-1434/article/view/260601
- DOI: https://doi.org/10.26442/18151434.2024.2.202803
- ID: 260601
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Introduction. Anti-PD-1 immunotherapy (IT) is becoming the standard treatment for patients with metastatic melanoma. However, immune checkpoint inhibitors are only effective in a fraction of patients, and studies examining biological markers and their correlation with clinical efficacy are insufficient to draw unambiguous conclusions.
Aim. To improve the outcomes of the first-line therapy for disseminated melanoma based on identifying clinical and immunohistochemical predictors of IT efficacy.
Materials and methods. Data from 130 patients who were treated with immune checkpoint inhibitors (nivolumab or prolgolimab) in the first-line therapy for disseminated melanoma between 2017 and 2024 were analyzed.
Results. Improvement was observed in 24 patients (18.4%): complete response in 18 patients (13.8%), partial response in 6 (4.6%), and stabilization in 71 (54.6%) patients. Progression was reported in 31 (24%) patients. Death occurred in 4 (3%) cases during IT with prolgolimab due to disease progression. The two-year disease-free survival (DFS) during IT was 53% (95% confidence interval [CI] 42–67), p=0.63; the median 2-year overall survival was not reached. In the immunohistochemical study, 47 (63.5%) patients had a predominance of tumor infiltration with CD8 lymphocytes over CD4, regardless of the IT type: 2-year DFS 82% (95% CI 70–96) vs 13% (95% CI 2.7–64) in the absence of CD8 predominance over CD4, p=0.0001; the median DFS was not reached in patients with the predominance of CD8 lymphocytes tumor infiltration over CD4 compared to the other group – 7.6 months in the absence of this feature (95% CI 5.8–0), p=0.001. The peritumoral location of the immune lymphoid infiltrate was observed in all 74 (100%) patients, and the intratumoral location was less common (52 patients, 70%). In the presence of both periand intratumoral location of the immune infiltrate, the 2-year DFS was 83% (95% CI 70–98) compared to the group of patients in whom no intratumoral location was detected – 5.5% (95% CI 0.8–36), p<0.0001. The expression of programmed cell death ligand 1 (PD-L1) level >10% was observed in 47 (63.5%) patients. With this level of PD-L1 expression, the one-year DFS was 91% (95% CI 83–100) compared to 29% (95% CI 15–57) with a lower level of PD-L1 expression, p<0.0001; the median DFS is reached, and in the group 2, DFS was only 6.6 months. In the case of PD-L1>10%, the 2-year DFS was high at 78% (95% CI 63–100), p<0.0001.
Conclusion. Based on the study's results, it can be assumed that immunohistochemical characteristics such as a PD-L1 expression level >10%, the simultaneous presence of periand intratumoral lymphoid tumor infiltration, and the predominance of CD8 over CD4 can be considered predictors of IT efficacy with nivolumab and prolgolimab.
作者简介
Liana Oganesyan
Russian Medical Academy of Continuous Professional Education; Loginov Moscow Clinical Scientific Center
编辑信件的主要联系方式.
Email: liana15.94@mail.ru
ORCID iD: 0000-0001-7564-7472
Graduate Student
俄罗斯联邦, Moscow; MoscowLarisa Zavalishina
Russian Medical Academy of Continuous Professional Education
Email: liana15.94@mail.ru
ORCID iD: 0000-0002-0677-7991
D. Sci. (Biol.)
俄罗斯联邦, MoscowNikolai Ognerubov
Penza Institute for Further Training of Physicians – branch of the Russian Medical Academy of Continuous Professional Education
Email: ognerubov_n.a@mail.ru
ORCID iD: 0000-0003-4045-1247
SPIN 代码: 3576-3592
D. Sci. (Med.), Prof., Cand. Sci. (Law)
俄罗斯联邦, PenzaIuliia Kostalanova
Samara State Medical University; Samara Regional Clinical Oncology Dispensary
Email: liana15.94@mail.ru
ORCID iD: 0000-0001-7395-0136
Cand. Sci. (Med.)
俄罗斯联邦, Samara; SamaraAndrey Orlov
Samara State Medical University; Samara Regional Clinical Oncology Dispensary; Ministry of Healthcare of Samara Region
Email: liana15.94@mail.ru
ORCID iD: 0000-0001-6145-3343
D. Sci. (Med.), Prof.
俄罗斯联邦, Samara; Samara; SamaraIrina Poddubnaya
Russian Medical Academy of Continuous Professional Education
Email: ivprectorat@inbox.ru
ORCID iD: 0000-0002-0995-1801
D. Sci. (Med.), Prof., Acad. RAS
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