Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma.
Ann Surg Oncol
; 27(11): 4122-4130, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32488521
ABSTRACT
BACKGROUND:
The frequency of "exhausted" or checkpoint-positive (PD-1+CTLA-4+) cytotoxic lymphocytes (Tex) in the tumor microenvironment is associated with response to anti-PD-1 therapy in metastatic melanoma. The current study determined whether pretreatment Tex cells in locally advanced melanoma predicted response to neoadjuvant anti-PD-1 blockade.METHODS:
Pretreatment tumor samples from 17 patients with locally advanced melanoma underwent flow cytometric analysis of pretreatment Tex and regulatory T cell frequency. Patients who met the criteria for neoadjuvant checkpoint blockade were treated with either PD-1 monotherapy or PD-1/CTLA-4 combination therapy. Best overall response was evaluated by response evaluation criteria in solid tumors version 1.1, with recurrence-free survival (RFS) calculated by the Kaplan-Meier test. The incidence and severity of adverse events were tabulated by clinicians using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.RESULTS:
Of the neoadjuvant treated patients, 10 received anti-PD-1 monotherapy and 7 received anti-CTLA-4/PD-1 combination therapy. Of these 17 patients, 12 achieved a complete response, 4 achieved partial responses, and 1 exhibited stable disease. Surgery was subsequently performed for 11 of the 17 patients, and 8 attained a complete pathologic response. Median RFS and overall survival (OS) were not reached. Immune-related adverse events comprised four grade 3 or 4 events, including pneumonitis, transaminitis, and anaphylaxis.CONCLUSION:
The results showed high rates of objective response, RFS, and OS for patients undergoing immune profile-directed neoadjuvant immunotherapy for locally advanced melanoma. Furthermore, the study showed that treatment stratification based upon Tex frequency can potentially limit the adverse events associated with combination immunotherapy. These data merit further investigation with a larger validation study.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article