Clinical Predictors of Response to Anti-PD-1 First-Line Treatment in a Single-Centre Patient Cohort: A Real-World Study

F R Di Pietro; S Verkhovskaia; S Mastroeni; M L Carbone; D Abeni; C Z Di Rocco; N Samà; A R Zappalà; P Marchetti; F De Galitiis; C M Failla; C Fortes

doi:10.1016/j.clon.2021.09.006

Clinical Predictors of Response to Anti-PD-1 First-Line Treatment in a Single-Centre Patient Cohort: A Real-World Study

Clin Oncol (R Coll Radiol). 2022 Jan;34(1):e18-e24. doi: 10.1016/j.clon.2021.09.006. Epub 2021 Sep 23.

Authors

F R Di Pietro¹, S Verkhovskaia¹, S Mastroeni², M L Carbone³, D Abeni², C Z Di Rocco¹, N Samà¹, A R Zappalà¹, P Marchetti⁴, F De Galitiis¹, C M Failla⁵, C Fortes²

Affiliations

¹ Department of Oncology and Dermatological Oncology, IDI-IRCCS, Rome, Italy.
² Epidemiology Unit, IDI-IRCCS, Rome, Italy.
³ Laboratory of Experimental Immunology, IDI-IRCCS, Rome, Italy.
⁴ Department of Clinical and Molecular Medicine, Oncology Unit, Sant'Andrea Hospital, Sapienza University, Rome, Italy; Medical Oncology Unit B, Policlinico Umberto I, Sapienza University, Rome, Italy.
⁵ Laboratory of Experimental Immunology, IDI-IRCCS, Rome, Italy. Electronic address: c.failla@idi.it.

PMID: 34563446
DOI: 10.1016/j.clon.2021.09.006

Abstract

Aims: Cutaneous melanoma is one of the most immunogenic tumours. Immunotherapy with checkpoint inhibitors, such as anti-PD-1 antibodies, has significantly improved the prognosis in metastatic melanoma. However, only half of the patients respond to this therapy and have a favourable outcome. Identifying factors associated with treatment failure and early identification of responders are both important to select the best treatment approach for each patient. The aim of our study was to investigate clinical biomarkers of response to treatment with anti-PD-1 antibodies.

Materials and methods: We selected all patients with stage IV melanoma (n = 147), subjected to first-line treatment with anti-PD-1 in the last 10 years. We investigated the associations between patients' different clinical features and progression-free survival, using the Cox proportional hazards models.

Results: In the multivariate analysis, an increased risk of disease progression was observed among patients with stage M1d metastases (hazard ratio 3.30; 95% confidence interval 1.58-6.91), compared with patients with stage M1a-M1b. Moreover, the risk of progression was greater in patients with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 (hazard ratio 2.04; 95% confidence interval 1.02-4.06) and in patients with ECOG PS ≥ 2 (hazard ratio 2.19; 95% confidence interval 1.05-4.55) compared with ECOG PS 0. High levels of lactate dehydrogenase (hazard ratio 2.06; 95% confidence interval 1.18-3.59) and the presence of respiratory diseases (hazard ratio 4.14; 95% confidence interval 1.42-12.0) at the beginning of anti-PD-1 treatment were also associated with an increased risk of disease progression. In a subgroup analysis, neutrophil count and neutrophil/lymphocyte ratio before anti-PD-1 treatment were higher in patients who underwent disease progression.

Conclusion: In our study population, independent predictors of disease progression among patients treated with first-line anti-PD-1 were as follows: ECOG PS, staging, lactate dehydrogenase and the presence of respiratory diseases.

Keywords: Biomarkers; PD-1; checkpoint inhibitors; immunotherapy; melanoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Immunotherapy
Melanoma* / drug therapy
Prognosis
Progression-Free Survival
Retrospective Studies
Skin Neoplasms* / drug therapy