scholarly journals Current Status and Prospects of Immunotherapy for Gynecologic Melanoma

2021 ◽  
Vol 11 (5) ◽  
pp. 403
Author(s):  
Mayuka Anko ◽  
Yusuke Kobayashi ◽  
Kouji Banno ◽  
Daisuke Aoki
Keyword(s):  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Treatment Options ◽  
Case Series ◽  
Current Status ◽  
Kit Mutation

Gynecologic melanomas are rare and have a poor prognosis. Although immunotherapy (immune checkpoint inhibitors) and targeted therapy has greatly improved the systemic treatment of cutaneous melanoma (CM) in recent years, its efficacy in gynecologic melanomas remains uncertain because of the rarity of this malignancy and its scarce literature. This review aimed to evaluate the literature of gynecologic melanomas treated with immunotherapy and targeted therapy through a PubMed search. We identified one study focusing on the overall survival of gynecologic melanomas separately and five case series and nine case reports concentrating on gynecologic melanomas treated with an immune checkpoint inhibitor and/or targeted therapy. Furthermore, the KIT mutation has the highest rate among all mutations in mucosal melanoma types. The KIT inhibitors (Tyrosine kinase inhibitors: TKIs) imatinib and nilotinib could be the treatment options. Moreover, immune checkpoint inhibitors combined with KIT inhibitors may potentially treat cases of resistance to immune checkpoint inhibitors. However, because of the different conditions and a small number of cases, it is difficult to evaluate the efficacy of immunotherapy and targeted therapy for gynecologic melanoma rigorously at this time. Further prospective cohort or randomized trials of gynecologic melanoma alone are needed to assess the treatment with solid evidence.

Targeted therapies and checkpoint inhibitors in sarcoma

QJM ◽  
2021 ◽  
Author(s):  
M Vasella ◽  
E Gousopoulos ◽  
M Guidi ◽  
G Storti ◽  
S Y Song ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Suppressor Gene ◽  
Treatment Practice ◽  
Therapeutic Concepts

Abstract Sarcomas are defined as a group of mesenchymal malignancies with over 100 heterogeneous subtypes. As a rare and difficult to diagnose entity, micrometastasis is already present at the time of diagnosis in many cases. Current treatment practice of sarcomas consists mainly of surgery, (neo)adjuvant chemo- and/or radiotherapy. Although the past decade has shown that particular genetic abnormalities can promote the development of sarcomas, such as translocations, gain-of-function mutations, amplifications or tumor suppressor gene losses, these insights have not led to established alternative treatment strategies so far. Novel therapeutic concepts with immunotherapy at its forefront have experienced some remarkable success in different solid tumors while their impact in sarcoma remains limited. In this review, the most common immunotherapy strategies in sarcomas, such as immune checkpoint inhibitors, targeted therapy and cytokine therapy are concisely discussed. The programmed cell death (PD)-1/PD-1L axis and apoptosis-inducing cytokines, such as TNF-related apoptosis-inducing ligand (TRAIL), have not yielded the same success like in other solid tumors. However, in certain sarcoma subtypes, e.g. liposarcoma or undifferentiated pleomorphic sarcoma, encouraging results in some cases when employing immune checkpoint inhibitors in combination with other treatment options were found. Moreover, newer strategies such as the targeted therapy against the ancient cytokine macrophage migration inhibitory factor (MIF) may represent an interesting approach worth investigation in the future.

scholarly journals Immune checkpoint inhibitor-induced aseptic meningitis and encephalitis: a case-series and narrative review

2021 ◽  
Vol 12 ◽  
pp. 204209862110047
Author(s):  
Laure Thouvenin ◽  
Timothée Olivier ◽  
Giuseppe Banna ◽  
Alfredo Addeo ◽  
Alex Friedlaender
Keyword(s):  
Adverse Events ◽  
Aseptic Meningitis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Case Series ◽  
Plain Language ◽  
Wide Range

Background: Along with the increasing use of immune checkpoint inhibitors comes a surge in immune-related toxicity. Here, we review the currently available data regarding neurological immune adverse events, and more specifically aseptic meningitis and encephalitis, and present treatment and diagnostic recommendations. Furthermore, we present five cases of immunotherapy-induced aseptic meningitis and encephalitis treated at our institution. Recent findings: Neurological immune-related adverse events, including aseptic meningitis and encephalitis, secondary to checkpoint inhibitors are a rare but complex and clinically relevant entity, comprising a wide range of diseases, most often presenting with symptoms with a wide range of differential diagnoses. Our case-series highlights the challenges of such entities and the importance of properly identifying and managing aseptic meningitis and encephalitis. Summary: Checkpoint inhibitor-induced meningoencephalitis warrants prompt investigations and treatment. Properly diagnosing aseptic meningitis, encephalitis, or mixed presentations may guide the treatment decision, as highlighted by our case-series. After rapid exclusion of alternative diagnoses, urgent corticosteroids are the therapeutic backbone but this could change in favour of highly specific cytokine-directed treatment options. Plain language summary Aseptic meningitis and encephalitis with immune checkpoint inhibitors: a single centre case-series and review of the literature Over the course of the past decade, checkpoint inhibitors have revolutionized cancer care. With their favourable toxicity profile and potential for durable and deep responses, they have become ubiquitous across the field of oncology. Furthermore, combination checkpoint inhibitors are also gaining ground, with increased efficacy and, unfortunately, immune-related toxicity. While there are guidelines based on extensive clinical experience for frequent adverse events, uncommon entities are less readily identified and treated. Neurological immune-related adverse events secondary to checkpoint inhibitors are a rare but complex entity, comprising a wide range of diseases, most often presenting with aspecific symptoms. In this paper, we discuss a single institution case-series of patients with autoimmune aseptic meningitis and encephalitis, and we perform a narrative literature review on this subject. We conclude with our treatment recommendations based on available evidence.

scholarly journals Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

2019 ◽  
Vol 12 (1) ◽  
pp. 260-276 ◽  
Author(s):  
Nikhil Agrawal ◽  
Arjun Khunger ◽  
Pankit Vachhani ◽  
Teresa A. Colvin ◽  
Alexander Hattoum ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Troponin I ◽  
Cardiac Toxicity ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Fulminant Myocarditis ◽  
Comprehensive Cancer Center ◽  
Cancer Center

The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced stage cancers. However, immune-related adverse events are frequently observed. Cardiac toxicity from ICI therapy can range from asymptomatic troponin-I elevations to conduction abnormalities of the heart and even fulminant myocarditis. Although rare, myocarditis is a potentially fatal adverse effect of ICI therapy. We present a series of five cases of ICI-related cardio-toxicity diagnosed and managed at Roswell Park Comprehensive Cancer Center along with a review of published case reports in the literature. Our series highlights the importance of high clinical suspicion, early diagnosis of myocarditis, and prompt initiation of immunosuppressive therapy.

Safety and Efficacy of Immune Checkpoint Inhibitors in Children and Young Adults with Haematological Malignancies: Review and Future Perspectives

2021 ◽  
Vol 19 ◽  
Author(s):  
Eleni Tsotridou ◽  
Eleni Vasileiou ◽  
Elpis Mantadakis ◽  
Athanasios Tragiannidis
Keyword(s):  
Clinical Trials ◽  
Young Adults ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Safety Data ◽  
Case Series ◽  
Great Promise ◽  
Haematological Malignancies

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blockade of inhibitory receptors and have shown great promise in preclinical models and studies in the adult population. However, paediatric malignancies present unique features and so far, experience with these agents remains limited. In the current review we present an overview of efficacy and safety data from case reports, case series and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

scholarly journals Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

2019 ◽  
Vol 14 (3) ◽  
pp. 273-283
Author(s):  
Amy Lee ◽  
Fa-Chyi Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Research Trend ◽  
Advanced Hcc

AbstractIn terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

Immune checkpoint inhibitors for advanced or metastatic basal cell carcinoma: how much evidence do we need?

Immunotherapy ◽  
2021 ◽  
Author(s):  
Elissar Moujaess ◽  
Reine Merhy ◽  
Joseph Kattan ◽  
Anne-Sophie Sarkis ◽  
Roland Tomb
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Unmet Need ◽  
Case Series ◽  
Metastatic Basal Cell Carcinoma

Basal cell carcinoma (BCC) is one of the most frequent and most curable tumors at its early stages. BCC rarely metastasizes and its treatment in this setting is still challenging. Hedgehog inhibitors showed an activity in advanced or metastatic disease. However, there is an unmet need for new agents. Immune checkpoint inhibitors have been assessed in melanoma and other cutaneous tumors, and very recently an anti-PD1 was approved for advanced BCC. In this paper, available data are reviewed on experimental and preclinical studies evaluating immunotherapy in BCC, as well as on the clinical evidence supporting the efficacy and safety of immune checkpoint inhibitors for advanced or metastatic BCC based on case reports, case series and clinical trials.

scholarly journals Perspective of Immune Checkpoint Inhibitors in Thymic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1065
Author(s):  
Kyoichi Kaira ◽  
Hisao Imai ◽  
Hiroshi Kagamu
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thymic Carcinoma ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Objective Response ◽  
Experimental Studies ◽  
Case Series ◽  
Phase Ii Studies ◽  
Dismal Prognosis

Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma. In our review, three prospective phase II studies and several case series were discussed in thymic carcinoma. We found that the objective response rate, disease control rate, and progression-free survival in PD-1 blockade monotherapy were approximately 20%, 73%, and four months, respectively. Two exploratory investigations indicated that PD-L1 within tumor cells exhibits a possibility of the therapeutic prediction of PD-1 blockade in thymic carcinoma. Several case reports, alongside their treatment content, have also been reviewed. The therapeutic efficacy of PD-1 blockade monotherapy is still limited in patients with thymic carcinoma. Future perspectives focus on the therapeutic implication of tyrokinase inhibitors plus ICIs or new experimental agents plus ICIs alongside several ongoing experimental studies.

scholarly journals Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Revati Sharma ◽  
Elif Kadife ◽  
Mark Myers ◽  
George Kannourakis ◽  
Prashanth Prithviraj ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanisms ◽  
Number Of Patients ◽  
Angiogenesis Pathway

AbstractVascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies.

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