Clinical Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Malignant Peritoneal Mesothelioma.
Ontology highlight
ABSTRACT:
SUBMITTER: Raghav K
PROVIDER: S-EPMC8346939 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
Publications
Clinical Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Malignant Peritoneal Mesothelioma.
Raghav Kanwal K Liu Suyu S Overman Michael M Morani Ajaykumar A Willette Anneleis A Fournier Keith K Varadhachary Gauri G
JAMA network open 20210802 8
Similar Datasets
Project description:Malignant pleural mesothelioma (MPM) is a malignant tumor with strong invasiveness, low survival rate and lack of effective treatment options. As the only first-line treatment plan for the advanced MPM, combination of pemetrexed and cisplatin chemotherapy have been existing since the last 20 years. Immunotherapy has long been considered as a potential treatment plan for MPM, mainly including immune checkpoint inhibitors (ICIs), immunotoxin therapy, anti-cancer vaccine and adoptive T-cell therapy. This review focuses on summarizing the current research status of immune checkpoint inhibitors in MPM, discusses the effect of tumor heterogeneity on ICIs treatment, and describes that the biomarker-oriented immunotherapy is a new vision for the realization of individualized treatment of MPM.
.
| S-EPMC8246391 | biostudies-literature
Project description:IntroductionMononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors.MethodsCase series of three patients with mononeuritis multiplex-all with mesothelioma-identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015-October 2022) set up to collect and investigate n-irAEs on a nationwide level.ResultsThree patients (male; median age 86 years; range 72-88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration.DiscussionWe report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event.
| S-EPMC10850347 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is a rare cancer usually caused by asbestos exposure and associated with a very poor prognosis. After more than a decade without new therapeutic options, immune checkpoint inhibitors (ICIs) demonstrated superiority over standard chemotherapy, with improved overall survival in the first and later-line settings. However, a significant proportion of patients still do not derive benefit from ICIs, highlighting the need for new treatment strategies and predictive biomarkers of response. Combinations with chemo-immunotherapy or ICIs and anti-VEGF are currently being evaluated in clinical trials and might change the standard of care in the near future. Alternatively, some non-ICI immunotherapeutic approaches, such as mesothelin targeted CAR-T cells or denditric-cells vaccines, have shown promising results in early phases of trials and are still in development. Finally, immunotherapy with ICIs is also being evaluated in the peri-operative setting, in the minority of patients presenting with resectable disease. The goal of this review is to discuss the current role of immunotherapy in the management of malignant pleural mesothelioma, as well as promising future therapeutic directions.
| S-EPMC10003250 | biostudies-literature
Project description: Not available
| S-EPMC11536716 | biostudies-literature
Project description:BackgroundStandard treatment for malignant peritoneal mesothelioma has not been established, and systemic chemotherapy is administered according to malignant pleural mesothelioma. We previously reported the efficacy of cisplatin plus pemetrexed as first-line chemotherapy; however, the efficacy of second-line chemotherapy remains unknown.MethodsWe retrospectively evaluated patients with malignant peritoneal mesothelioma who started first-line systemic chemotherapy with platinum plus pemetrexed between March 2007 and February 2019 at the National Cancer Center Hospital. Patients who received second-line chemotherapy after failure of platinum plus pemetrexed were identified. We evaluated the efficacy of first- and second-line chemotherapy, and explored the prognostic factors. Survival outcomes were estimated using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models.ResultsA total of 54 and 26 patients received platinum plus pemetrexed as first- and second-line chemotherapy, respectively (gemcitabine in 12 patients; taxane, six; nivolumab, three; and others, five). In all patients, the median overall survival and progression-free survival after first-line chemotherapy were 16.6 and 7.3 months, respectively. Among patients who received second-line chemotherapy, the median overall survival, progression-free survival, and second-line overall survival were 16.9, 3.2, and 9.9 months, respectively. Patients who received ≥6 cycles of platinum plus pemetrexed as first-line chemotherapy had longer overall survival after second-line chemotherapy than those who did not (hazard ratio, 0.23; 95% confidence interval: 0.06-0.82; p = 0.02).ConclusionsSecond-line chemotherapy may be an option for refractory malignant peritoneal mesothelioma, especially in patients who have completed 6 cycles of platinum plus pemetrexed as first-line chemotherapy.
| S-EPMC7980334 | biostudies-literature
Project description:Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (p < 0.001 and p = 0.006, respectively) or anti CTLA-4 (p < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13−27%) and 56% (95% CI 45−67%), respectively, and they did not significantly differ between combined and single agent treatments (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted.
| S-EPMC9775536 | biostudies-literature
Project description:Platinum-based chemotherapy is commonly used as the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM). However, in recent times, immune-checkpoint inhibitors (ICIs) have led to a paradigm shift. Herein, we review relevant literature and ongoing trials of ICIs used as both first-line and salvage therapies. Specifically, in the Japanese single-arm, phase II trial, the MERIT trial, nivolumab, an antiprogrammed cell death 1 (PD-1) antibody showed favorable efficacy when used as a salvage therapy. Currently, multiple ICI monotherapy or combination therapy trials have been conducted, which could provide further evidence. Among available ICIs, the anti-PD-1 antibody is promising for unresectable MPM, despite the limited efficacy of anti-CTLA4 monotherapy. Ongoing studies will further confirm the potential efficacy of ICIs for MPM, as observed across other malignancies. It is also crucial to identify any clinically useful predictive biomarkers that could reveal ICIs with maximal effects in MPM.
| S-EPMC7057421 | biostudies-literature
Project description:Malignant mesothelioma (MM) is a rare and aggressive neoplasm, usually associated with a poor prognosis (5 years survival rate <10%). For unresectable disease, platinum and pemetrexed chemotherapy has been the only standard of care in first line for more than two decades, while no standard treatments have been approved in subsequent lines. Recently, immunotherapy has revolutionized the therapeutic landscape of MM. In fact, the combination of ipilimumab plus nivolumab has been approved in first line setting. Moreover, immune checkpoint inhibitors (ICIs) showed promising results also in second-third line setting after platinum-based chemotherapy. Unfortunately, approximately 20% of patients are primary refractory to ICIs and there is an urgent need for reliable biomarkers to improve patient's selection. Several biological and molecular features have been studied for this goal. In particular, histological subtype (recognized as prognostic factor for MM and predictive factor for chemotherapy response), programmed death ligand 1 (PD-L1) expression, and tumor mutational burden (widely hypothesized as predictive biomarkers for ICIs in several solid tumors) have been evaluated, but with unconclusive results. On the other hand, the deep analysis of tumor infiltrating microenvironment and the improvement in genomic profiling techniques has led to a better knowledge of several mechanisms underlying the MM biology and a greater or poorer immune activation. Consequentially, several potential biomarkers predictive of response to immunotherapy in patients with MM have been identified, also if all these elements need to be further investigated and prospectively validated. In this paper, the main evidences about clinical efficacy of ICIs in MM and the literature data about the most promising predictive biomarkers to immunotherapy are reviewed.
| S-EPMC9911663 | biostudies-literature
Project description:Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence analyses on tissue microarrays (n = 3) from patients with malignant pleural mesothelioma (MPM, n = 88) and malignant peritoneal mesothelioma (MPeM, n = 25). Our study aimed to elucidate spatial distributions of key immune cell populations and their association with lymphocyte activation gene 3 (LAG3), BRCA1-associated protein 1 (BAP1), neurofibromatosis type 2 (NF2), and methylthioadenosine phosphorylase (MTAP), with MTAP serving as a cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/B) surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types and prognosis and clinical characteristics of patients with malignant mesothelioma. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared with MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared with those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma, containing hematoxylin and eosin and multiplex immunofluorescence images with corresponding metadata.SignificanceConsidering the limited therapeutic options available to patients with malignant mesothelioma, there is substantial translational potential in understanding the correlation between the spatial architecture of the malignant mesothelioma tumor immune microenvironment and tumor biology. Our investigation reveals critical cell-cell interactions that may influence the immune response against malignant mesothelioma tumors, potentially contributing to the differential behaviors observed in MPM and MPeM. These findings represent a valuable resource for the malignant mesothelioma cancer research community.
| S-EPMC11328914 | biostudies-literature
Project description:Background: Immune checkpoint inhibitors (ICIs) are approved as cancer immunotherapeutic agents for advanced malignant melanoma (MM) in recent years, and nivolumab and ipilimumab are the most widely used ICIs either alone or in combination. However, their efficacy and safety between single and combined ICIs are not clear. This meta-analysis (MA) is aimed to update the efficacy and safety of ICIs by comparing monotherapy and combination therapy in the treatment of advanced MM. Method: We searched PubMed, Embase, EbscoHost and ClinicalTrials.gov for the eligible randomized controlled trials (RCTs) which compared the efficacy and safety of ICIs between a single ICI and combined ICIs. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on the study heterogeneity. Results: A total of nine RCTs were included in this MA. Regarding the efficacy, combined nivolumab and ipilimumab therapy showed statistically significant prolonged OS and PFS with HR 0.65, 95% CI [0.53, 0.79], p <0.0001 and HR 0.48, 95% CI [0.38, 0.60], p<0.0001 respectively. Combination therapy with nivolumab and ipilimumab also showed statistically significant longer ORR than monotherapy; with RR 2.15, 95% CI [1.63, 2.84], p <0.00001. In terms of safety, the incidence of all AEs which include any AEs, high-grade, haematological, gastrointestinal, dermatological, pulmonary, liver and endocrine AEs were significantly lower with monotherapy (either nivolumab or ipilimumab) of ICI compared to combination ICI therapy with a p-value <0.00001 to 0.03. Conclusion: Efficacy of the combined nivolumab and ipilimumab was better than a single ICI, especially in the treatment of advanced MM. Although combination therapy showed better efficacy than monotherapy, monotherapy (either nivolumab or ipilimumab) was safer than combination therapy as it tended to decrease the incidence of most of the treatment-related AEs.
| S-EPMC9414012 | biostudies-literature