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

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.

The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

“…More than half of the studies were reported from the Far East (n = 15) (Ichiki et al, 2019;Jiang et al, 2020;Kitadai et al, 2020;Takada et al, 2020;Ke et al, 2021;Morimoto et al, 2021;Ng et al, 2021;Pu et al, 2021;Sato et al, 2021;Tokuyama et al, 2021;Chen et al, 2022;Kim et al, 2022;Li et al, 2022;Wu et al, 2022;Zhang et al, 2022), followed by Europe (n = 12) (Dercle et al, 2016;Bigot et al, 2017;Mezquita et al, 2018;Svaton et al, 2018;Cantini et al, 2020;Awada et al, 2021;Onn et al, 2021;Ruiz-Bañobre et al, 2021;Stares et al, 2021;Assié et al, 2022;Schneider et al, 2022;Stares et al, 2022). A 3.5 gr/dL albumin cut-off was most frequently used in the included studies (n = 20) (Dercle et al, 2016;Bigot et al, 2017;Mezquita et al, 2018;Formica et al, 2020;Jiang et al, 2020;Kitadai et al, 2020;Lee et al, 2020;Takada et al, 2020;Awada et al, 2021;Brown et al, 2021;Khaki et al, 2021;Morimoto et al, 2021;Ng et al, 2021;Onn et al, 2021;…”

“…Thirty-four studies were included in the analyses for OS (Stroup et al, 2000;Dercle et al, 2016;Bigot et al, 2017;Mezquita et al, 2018;Svaton et al, 2018;Ichiki et al, 2019;Cantini et al, 2020;Formica et al, 2020;Jiang et al, 2020;Kitadai et al, 2020;Lee et al, 2020;Swami et al, 2020;Takada et al, 2020;Awada et al, 2021;Brown et al, 2021;de Kouchkovsky et al, 2021;Ke et al, 2021;Khaki et al, 2021;Morimoto et al, 2021;Ng et al, 2021;Onn et al, 2021;Pu et al, 2021;Ruiz-Bañobre et al, 2021;Sato et al, 2021;Stares et al, 2021;Tokuyama et al, 2021;Abuhelwa et al, 2022;Assié et al, 2022;Chen et al, 2022;Guo et al, 2022;Kim et al, 2022;Li et al, 2022;Stares et al, 2022;Wu et al, 2022;Yoo et al, 2022). In the meta-analysis, patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52-1.80, p < 0.0001) than patients with higher albumin levels (Figure 1).…”

Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

“…In recent years, related immunological studies have found that immune cell infiltration plays a key role in the tumor microenvironment in the formation, occurrence and development (31,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). The most concerned are the immune checkpoint protein PD-1 and its ligands PD-L1 and PDCD1LG2, tumor transforming growth factor B1 (TGFB1) and its receptors TGFB1R (48)(49)(50)(51)(52)(53)(54). TGFB1 plays an immunosuppressive role in the process of tumor progression.…”

The Genes–Stemness–Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints

“…Hypoxia, by acting via increased HIF1α-expression, induces PD-L1 expression in tumor cell lines as well as in murine macrophage and dendritic cells. In MPM, although being related to higher response rates to nivolumab [ 103 , 104 , 105 ], the increased PD1 and PD-L1 expression are mainly associated with sarcomatoid morphology and do not significantly affect overall survival [ 106 , 107 , 108 ]. This observation clearly points out that other parameters are involved with PD1 and PD-L1 in determining real sensitivity to immunotherapy in a complex and heterogeneous context as MPM, such as tumor mutational burden or tumor-infiltrating lymphocytes, the tumor-associated macrophages (TAMs), which are abundantly present in the MPM microenvironment and play an important role in inducing T-cell suppression, Tim-3 (T cell immunoglobulin and mucin-domain containing-3), which is a co-inhibitory receptor expressed on IFN-γ-producing T cells, FoxP3+ Treg cells, and innate immune cells (macrophages and dendritic cells), T-regulatory cells [ 88 , 109 , 110 , 111 , 112 ].…”