bims-mesote 2026-03-01 papers

Issue of 2026–03–01
three papers selected by
Laura Mannarino, Humanitas Research

Curr Oncol. 2026 Feb 03. pii: 93. [Epub ahead of print]33(2):

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: Efficacy, Real-World Outcomes, and the Search for Predictive Biomarkers.

Giusi Bondì, Serafina Martella, Dimitrios Stylianakis, Alberto Terminella, Filippo Lococo, Alessia Ciarrocchi, Alfonso Fiorelli, Giacomo Cusumano.

Immunotherapy has significantly reshaped the management of malignant pleural mesothelioma (MPM), offering new therapeutic opportunities after decades in which platinum-pemetrexed chemotherapy represented the only systemic option. However, clinical benefit remains markedly heterogeneous, with outcomes strongly influenced by histologic subtype, patient characteristics, and real-world treatment conditions. Evidence from monotherapy trials has been inconsistent, whereas combination approaches-particularly nivolumab plus ipilimumab-have demonstrated improved survival compared with chemotherapy, mainly in non-epithelioid tumors. Nevertheless, real-world data consistently show lower efficacy and higher toxicity than registrational studies, especially among elderly and unselected populations. Recent translational work has highlighted the relevance of the tumor microenvironment and recurrent genomic alterations such as BAP1, NF2, and CDKN2A in shaping immune activity and potentially modulating response to immune checkpoint inhibitors. Transcriptomic signatures and circulating biomarkers-including soluble mesothelin-related peptide-have shown prognostic associations but no validated predictive value. Overall, current evidence suggests that sensitivity to immunotherapy in MPM arises from a complex interplay of genomic, immunologic, and clinical factors, and that no biomarker is yet suitable for guiding treatment decisions. Prospective studies integrating molecular and immune profiling will be essential to refine patient selection and advance toward a more rationally personalized use of immunotherapy.

Keywords: biomarkers; genomic alterations; immune checkpoint inhibitors; immunotherapy outcomes; malignant pleural mesothelioma; tumor microenvironment

DOI: https://doi.org/10.3390/curroncol33020093

Cancers (Basel). 2026 Feb 19. pii: 679. [Epub ahead of print]18(4):

Clinical Importance of Molecular Biomarkers in Pleural Mesothelioma.

Logan Roof, Kenna Koehler, Claire Verschraegen.

Pleural mesothelioma (PM) is a rare malignancy with opportunities for improvement in current treatment paradigms despite recent advances in systemic therapy. While histology remains the most clinically relevant prognostic indicator, the expanding use of immunotherapy and ongoing clinical trials involving targeted therapies have increased interest in the development of predictive and prognostic biomarkers in this disease. This review summarizes the current biologic and therapeutic landscape of PM and the biomarkers that influence prognosis and treatment response. Biomarkers such as programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) demonstrate inconsistent predictive value in PM and are not currently used in clinical decision pathways in the real-world setting. This review highlights the developing role of dynamic biomarkers such as circulating tumor DNA (ctDNA) for molecular response assessment and minimal residual disease (MRD) detection. This review also examines important genomic and transcriptomic alterations in PM, such as MTAP, BAP1, CDKN2A, and NF2/YAP/TEAD. These alterations provide potential targets for ongoing early-phase clinical trials. Future advances in PM will depend on the development and integration of comprehensive biomarker models that combine clinicopathologic, immune, and molecular features of this complex and heterogenous disease.

Keywords: immunotherapy; pleural mesothelioma; precision medicine; predictive biomarkers; prognostic biomarkers

DOI: https://doi.org/10.3390/cancers18040679

J Clin Oncol. 2026 Feb 24. JCO2501328

Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743.

In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses with first-line nivolumab plus ipilimumab versus chemotherapy. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomly assigned patients (5-year OS rates, 14% v 6%; hazard ratio [HR], 0.74 [95% CI, 0.62 to 0.88]); similar benefit was observed regardless of tumor histology. Of biomarker-evaluable patients treated with nivolumab plus ipilimumab (n = 242), high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS versus low M-MDSC levels (HR, 1.25 [95% CI, 1.09 to 1.43]). After adjusting for 24% of patients in the chemotherapy arm who received subsequent immunotherapy, nivolumab plus ipilimumab demonstrated continued OS benefit versus chemotherapy (HR, 0.64 [95% CI, 0.53 to 0.78]). No new safety signals were observed. These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable PM.

DOI: https://doi.org/10.1200/JCO-25-01328