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 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.

scholarly journals Management of rheumatic complications of ICI therapy: a rheumatology viewpoint

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii49-vii58 ◽  
Author(s):  
Jan Leipe ◽  
Xavier Mariette
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Standard Of Care ◽  
Immunosuppressive Drugs ◽  
Anti Inflammatory

Abstract Since immune checkpoint inhibitors became the standard of care for an increasing number of indications, more patients have been exposed to these drugs and physicians are more challenged with the management of a unique spectrum of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors. Those irAEs of autoimmune or autoinflammatory origin, or both, can involve any organ or tissue, but most commonly affect the dermatological, gastrointestinal and endocrine systems. Rheumatic/systemic irAEs seem to be less frequent (although underreporting in clinical trials is probable), but information on their management is highly relevant given that they can persist longer than other irAEs. Their management consists of anti-inflammatory treatment including glucocorticoids, synthetic and biologic immunomodulatory/immunosuppressive drugs, symptomatic therapies as well as holding or, rarely, discontinuation of immune checkpoint inhibitors. Here, we summarize the management of rheumatic/systemic irAEs based on data from clinical trials but mainly from published case reports and series, contextualize them and propose perspectives for their treatment.

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 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.

Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Anastasios Kyriazoglou ◽  
Maria Kaparelou ◽  
Georgios Goumas ◽  
Michael Liontos ◽  
Roubini Zakopoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

<b><i>Introduction:</i></b> The clinical outcome of HER2-positive breast cancer patients changed with the use of anti-Her therapies, though it still remains an aggressive and fatal disease. Implementation of immune checkpoint inhibitors in HER2-positive Breast cancer is a concept supported by the reported biological and preclinical data. <b><i>Methods:</i></b> We conducted a systematic review of the current literature involving immune checkpoint inhibitors alone or in combination with targeted therapies or chemotherapy finalized or running in HER2-positive breast cancer. <b><i>Results:</i></b> Twelve clinical trials and 2 case reports were identified in our study. <b><i>Conclusion:</i></b> The reported clinical trials highlight that checkpoint inhibition seems to be promising in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer.

Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials

2021 ◽  
Vol 148 ◽  
pp. 76-91
Author(s):  
Elisa Agostinetto ◽  
Daniel Eiger ◽  
Matteo Lambertini ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Randomised Clinical Trials

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

scholarly journals Combinatorial benefit without synergy in recent clinical trials of immune checkpoint inhibitors

2020 ◽  
Author(s):  
Adam C. Palmer ◽  
Benjamin Izar ◽  
Peter K. Sorger
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Combination Therapies ◽  
Anti Tumor Activity

ABSTRACTHundreds of clinical trials are testing whether combination therapies can increase the anti-tumor activity of Immune Checkpoint Inhibitors (ICIs). We find that the benefits of recently reported and approved combinations involving ICIs are fully accounted for by increasing the chance of a single-agent response (drug independence), with no requirement for additive or synergistic efficacy. Thus, the degree of success of combinations involving ICIs with other therapies is largely predictable.

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