Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study

SIMPLE SUMMARY: Immune-checkpoint inhibitors have only been studied in clinical trials for second-line and now first-line malignant pleural mesothelioma. Sometimes, results found in clinical trials do not translate to real-life settings. We aim to study second-line and onward nivolumab in malignant pleural mesothelioma to verify its effectiveness in France. We enrolled 109 patients from 11 centers in France. Our study proves in multivariate analysis that nivolumab has an efficacy against MPM. An intermediate LIPI score seems predictive of good response, but less in those < 70 years and for the first time in biphasic subtype. Ancillary studies are needed to more deeply explore these findings. ABSTRACT: Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10–25% objective response rate (ORR) and 40–70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017–July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients’ characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2–5.9) and 12.8 (9.2–16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52–7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22–0.99), progression on the line preceding nivolumab: 2.1 (1.11–3.9) and age > 70 years: 2.5 (1.5–4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08–11.8) and albumin < 25 g/L: 10.28 (1.5–70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.