Open AccessImmunotherapeutic early-phase clinical trials and malignant gliomas: A single-center experience and comprehensive immunophenotyping of circulating leukocytes
Author(s) -
Matteo Simonelli,
Paola Persico,
Arianna Capucetti,
Claudia Carenza,
Sara Franzese,
Elena Lorenzi,
Angelo Dipasquale,
Agnese Losurdo,
Laura Giordano,
Federico Pessina,
P. Navarria,
Letterio S. Politi,
Domenico Mavilio,
Massimo Locati,
Silvia Della Bella,
Armando Santoro,
Raffaella Bonecchi
Publication year - 2021
Publication title -
neuro-oncology advances
Language(s) - English
Resource type - Journals
ISSN - 2632-2498
DOI - 10.1093/noajnl/vdab160
Subject(s) - medicine , temozolomide , immunotherapy , oncology , clinical trial , immunophenotyping , univariate analysis , glioma , progression free survival , multivariate analysis , immunology , chemotherapy , antigen , cancer , cancer research
Background Immunotherapeutic early-phase clinical trials (ieCTs) increasingly adopt large expansion cohorts exploring novel agents across different tumor types. High-grade glioma (HGG) patients are usually excluded from these trials. Methods Data of patients with recurrent HGGs treated within multicohort ieCTs between February 2014 and August 2019 (experimental group, EG) at our Phase I Unit were retrospectively reviewed and compared to a matched control group (CG) of patients treated with standard therapies. We retrospectively evaluated clinical, laboratory, and molecular parameters through univariate and multivariate analysis. A prospective characterization of circulating leukocyte subpopulations was performed in the latest twenty patients enrolled in the EG, with a statistical significance cutoff of P < .1. Results Thirty HGG patients were treated into six ieCTs. Fifteen patients received monotherapies (anti-PD-1, anti-CSF-1R, anti-TGFβ, anti-cereblon), fifteen patients combination regimens (anti-PD-L1 + anti-CD38, anti-PD-1 + anti-CSF-1R). In the EG, median progression-free survival and overall survival (OS) from treatment initiation were 1.8 and 8.6 months; twelve patients survived more than 12 months, and two of them more than 6 years. Univariate analysis identified O6-methylguanine DNA methyltransferase (MGMT) promoter methylation and total protein value at six weeks as significantly correlated with a better outcome. Decreased circulating neutrophils and increased conventional dendritic cells levels lead to significantly better OS. Conclusions A subgroup of EG patients achieved remarkably durable disease control. MGMT promoter methylation identifies patients who benefit more from immunotherapy. Monitoring dynamic changes of innate immune cell populations may help to predict clinical outcomes.