Immunotherapy experience in malignant pleural mesothelioma in a single tertiary center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20565-e20565
Author(s):  
Ervin Saúl Enciso López ◽  
Efrain Isaias Camarin Sanchez ◽  
Daniela Vazquez Juarez ◽  
Alejandro Noguez-Ramos ◽  
Daniela Shveid Gerson ◽  
...  

e20565 Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer. Prognosis is generally poor, with a median overall survival (mOS) of approximately 12 months. MPM appears to be directly linked to immunosuppressive mechanisms, leading to use of checkpoint inhibitors for patients with this disease. Methods: We performed a retrospective chart review of patients with MPM at our institution between January 2015 to December 2020. All patients were over 18 years at the time of diagnosis of mesothelioma, a total of 8 patients were retrieved from the pathology database of The American British Cowdray Medical Center. The clinical-pathologic features collected were sex, age, performance status, risk factors, pTNM stage (AJCC 8th edition), histology type, sintomatology of onset, metastases sites and treatment. Clinical response rate and other outcomes were assessed. Descriptive statistics were used to describe a patient's demographic and disease characteristics. Results: 8 patients, aged 49 to 71 years (median of 65) at diagnosis of MPM were treated in our center. Both sex presented 4 patients in total. An identifiable risk factor was recorded in 4 patients (2 with asbesto exposure and 2 with heavy smoking). 7 patients (87.5%) had PS 0 or 1, the remaining has PS 2. The clinical stage at diagnosis was unresectable in 7 patients. 3 patients were assessed with PD-L1 expression (SP263 or 22C3), only one with expression of 20%. All patients received at least one scheme of chemotherapy prior to receiving immunotherapy, 25% received bevacizumab/platinum/anti-folate agents. Checkpoint inhibitors were introduced as a second line in 20% and in 80% has a third or more lines. Pembrolizumab was used in 20% and Nivolumab in 80%. The tumor responses with immunotherapy were as follows: partial response 12.5%, stable disease 75% and progressive disease 12.5%. Median progression-free survival of the first line treatment was 18.9 months (4.6-33.6 months), and for the line with checkpoint inhibitors was 11.2 weeks (7-21.2). In the full cohort, mOS was 37.0 months (95% CI:14.5-39.6). According to histology, the mOS for epithelioid-type was 36.6 months and for biphasic-type was 14.6 months (p = 0.42). mOS was 37.0 months for the group with immunotherapy and 15.0 months for those with standard chemotherapy (p = 0.14). The most frequently reported immune mediated adverse events were hypothyroidism and colitis (each one with one patient). Conclusions: In this real-world analysis, mOS was superior to those obtained in the MAPS2 trial (mOS 11.9 months), despite the fact that 80% of the population that received immunotherapy was in third or more lines. Limitations include limited numbers of patients, retrospective review, single institution, and inclusión of many heavily pretreated patients. Also molecular and immunohistochemical results such as PD-L1 status were only available on a limited number of patients.

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Ryuichi Noda ◽  
Shunsuke Yanagisawa ◽  
Masato Inoue ◽  
Tetsuo Hara

BACKGROUNDMalignant pleural mesothelioma (MPM) is a rare cancer, and in 80% of cases the cause is asbestos exposure. In 1972, the World Health Organization (WHO) declared asbestos is a carcinogenic substance. Since then, every developed country has restricted and banned the product. Because of its high heat resistance, asbestos had been widely used as building material for decades. The WHO estimated that approximately 125 million people are exposed to asbestos, and more than 107,000 die from asbestos-related diseases annually. Because of its long incubation period, the number of patients is estimated to keep increasing in the near future.OBSERVATIONSThe authors report a case of long-surviving MPM with a rushed clinical course after brain metastasis. A 69-year-old woman diagnosed with MPM (epithelial type) 6 years earlier presented with a brain metastasis. The pathological result of the brain metastasis was the sarcomatoid type. This case showed the possibility of subtype transition after long survival.LESSONSThis article aids in understanding the long-term natural history of MPM and the possibility of epithelial-mesenchymal transition. Neurosurgeons have to be aware of its the natural history and the possibility of brain metastasis.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20070-e20070
Author(s):  
Adithya Balasubramanian ◽  
Adrian Pick ◽  
Beena Kumar ◽  
Zdenka Prodanovic ◽  
Prashant Joshi ◽  
...  

e20070 Background: Malignant Pleural Mesothelioma (MPM) is a rare but fatal disease related to asbestos exposure, with historic survival in the order of 9 to 17 months. Chemotherapy is associated with only a modest benefit. The advent of immunotherapy has heralded significantly improved outcomes using checkpoint inhibitors in an as yet ill-defined cohort. We aim to identify predictive and prognostic biomarkers in a series of patients (pts) with MPM and describe survival data. Methods: A retrospective audit was undertaken of pts with MPM diagnosed between 2013 and 2017 at a single tertiary centre in Melbourne, Australia (Monash Health). Data relating to patient outcomes and clinicopathological features were obtained through medical reports. Further immunostains are being performed on archived tissue for PDL-1 status. Results: 65 pts were identified, of whom 52 (80.0%) were male. Median age was 73 years (range 44-90). 52 pts were noted to be ECOG 0-1. 42 pts (64.6%) were noted to have suspected asbestos exposure. Epithelioid MPM was the most common subtype, noted in 41 pts (63.1%) (table 1). 8 pts (12.3%) presented with stage IV disease. 16 pts (24.6%) received checkpoint inhibitor therapy, with 10 (63 %) in the second/third line setting. Median overall survival (OS) was 19.8 months (95% CI 13.3-26.3) in the whole cohort.Patient characteristics associated with poor OS were: presence of weight loss (P = 0.001), chest pain (p = 0.08) and ECOG 2 (p = 0.04). Pts with sarcomatoid histology who received immune checkpoint inhibitors in any line of treatment had significantly prolonged OS compared to other histologies. 3-year survival was 80% in this group while median OS was not reached (p = 0.04). This difference was not seen with other histologies. Conclusions: The evolving landscape of treatment in MPM appears to show promise in improving OS. In this unselected case series, our data is consistent with historic controls in terms of survival and prognostic factors. The finding of significantly improved survival with immune checkpoint inhibitors in the sarcomatoid histology is exciting and warrants further exploration. Further data on PDL1 status will be presented.


2019 ◽  
Vol 14 (9) ◽  
pp. e185-e187 ◽  
Author(s):  
Michael G. McCusker ◽  
Katherine A. Scilla ◽  
Charles B. Simone ◽  
Ashutosh Sachdeva ◽  
Kenneth D. Miller ◽  
...  

2018 ◽  
Author(s):  
Nicolas Alcala ◽  
Christophe Caux ◽  
Nicolas Girard ◽  
J.D. McKay ◽  
Francoise Galateau-Salle ◽  
...  

SummaryMalignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, which incidence is expected to increase in the future, and with no effective therapeutic options. We have performed unsupervised analyses of publicly available RNAseq data for 297 MPM. We found that the molecular profile and the prognosis of this disease is better explained by a continuous model rather than by the current WHO classification into the epitheloid, biphasic and sarcomatoid histological types. The main source of variation of this continuum was explained by the immune and vascular pathways, with strong differences in the expression of pro-angiogenic genes and immune checkpoint inhibitors across samples. These data may inform future classifications of MPM and may also guide personalised therapeutic approaches for this disease.SignificanceMalignant Pleural Mesothelioma (MPM) is an aggressive disease with no effective therapeutic options. Unsupervised transcriptomic analyses of 297 MPM unveiled the vascular and the immune systems as key players in the prognosis of this disease, and identified potential therapeutic approaches for this disease targeting these pathways.


2020 ◽  
Vol 13 (3) ◽  
pp. 1483-1489
Author(s):  
Bernard F. Hearon ◽  
Kyle N. Redelman ◽  
Georges C. Elhomsy ◽  
Dennis F. Moore, Jr.

The lead author with clinical stage I malignant pleural mesothelioma, epithelioid type, highly programmed cell death ligand 1 (PD-L1) positive, and BAP1 negative, experienced a prompt and exceptionally favorable response to pembrolizumab monotherapy. After cessation of treatment due to immune-related endocrinopathies, complete metabolic response on interim PET/CT scan was achieved. Two years after initial diagnosis, unifocal tumor reactivation was addressed with successful pembrolizumab monotherapy rechallenge. Immunotherapy, typically not used as frontline treatment for malignant pleural mesothelioma, may provide an effective and durable response for some patients. Based on this single case study, epithelioid type tumors with strongly positive PD-L1 and BAP1-negative immunohistochemical markers may be well suited for treatment with immune checkpoint inhibitors such as pembrolizumab.


Author(s):  
Giulio Metro ◽  
Diego Signorelli ◽  
Elio G. Pizzutilo ◽  
Laura Giannetta ◽  
Giulio Cerea ◽  
...  

2021 ◽  
Vol 9 (2) ◽  
pp. e001601
Author(s):  
Ania Alay ◽  
David Cordero ◽  
Sara Hijazo-Pechero ◽  
Elisabet Aliagas ◽  
Adriana Lopez-Doriga ◽  
...  

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify patients with MPM based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response.MethodsThe abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using gene set variation analysis. Identification of clinically relevant fractions was performed with Cox proportional-hazards models adjusted for age, stage, sex, and tumor histology. Immune-based groups were defined based on the identified fractions.ResultsT-helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. While no differential genomic alterations were identified among immune groups, at the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI.ConclusionsThis study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of patients with MPM with better prognosis and who might benefit from immune-based therapies. Molecular specificities of the different groups might be used to tailor specific potential therapies in the future.


Author(s):  
Anne S. Tsao ◽  
Harvey I. Pass ◽  
Andreas Rimner ◽  
Aaron S. Mansfield

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.


2022 ◽  
Vol 12 ◽  
Author(s):  
Moshe Lapidot ◽  
Srinivas Vinod Saladi ◽  
Ravi Salgia ◽  
Martin Sattler

Advances in the treatment of malignant pleural mesothelioma (MPM) have been disappointing, despite the apparent need for new therapeutic options for this rare and devastating cancer. Drug resistance is common and surgical intervention has brought benefits only to a subset of patients. MPM is a heterogenous disease with a surprisingly low mutation rate and recent sequencing efforts have confirmed alterations in a limited number of tumor suppressors that do not provide apparent insights into the molecular mechanisms that drive this malignancy. There is increasing evidence that epigenetic regulation leads to immune evasion and transformation in MPM. Further, the low efficacy of immune checkpoint inhibitors is consistent with a suppression of genes involved in the anti-tumor immune response. We review three promising emerging therapeutic targets (STAT3, KDM4A, heparanase) and highlight their potential effects on the immune response.


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