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 Hemophagocytic Lymphohistiocytosis Secondary to PD-1 and IDO Inhibition in a Patient with Refractory Glioblastoma

2020 ◽  
Vol 13 (2) ◽  
pp. 508-514
Author(s):  
Rohit Thummalapalli ◽  
Thatcher Heumann ◽  
Julie Stein ◽  
Sarah Khan ◽  
David S. Priemer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Altered Mental Status ◽  
Rapid Onset ◽  
History Of

Immune checkpoint inhibition (ICI)-based approaches have transformed the treatment landscape of numerous solid tumors. Glioblastoma (GBM) is an aggressive and almost universally fatal disease which is in need of novel treatment options, and combinations of immune checkpoint inhibitors, including dual agent therapy, are starting to be explored in refractory GBM. Growing adoption of ICI-based approaches in solid tumors has been met with improved understanding of immune-related adverse events (IRAEs), including primary hematologic adverse events. Although management guidelines for multiple hematologic IRAEs have been established, the emergence of hemophagocytic lymphohistiocytosis (HLH) secondary to ICI therapy has only rarely been described, and its pathogenesis and optimal management are incompletely understood. We present the case of a 74-year-old male with a history of refractory GBM treated with PD-1 and indoleamine-pyrrole 2,3-dioxygenase (IDO) inhibition who experienced acute liver injury, followed by progressive fevers, altered mental status, and cytopenias. Serum studies and examination of spleen and bone marrow pathology were consistent with HLH, which was refractory to steroids and ultimately resulted in his rapid clinical decline. Here, we review prior cases of HLH secondary to ICI therapy across solid tumors, and explore potential mechanisms contributing to the rapid onset and refractory nature of our patient’s HLH syndrome. We hope to further highlight HLH as an emerging hematologic IRAE secondary to ICI therapy, and suggest that new practice guidelines begin to recognize HLH as a characteristic hematologic IRAE in patients treated with PD-1 and other immune checkpoint inhibitors.

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.

scholarly journals A real‐world data of Immune checkpoint inhibitors in solid tumors from India

2021 ◽  
Author(s):  
Vanita Noronha ◽  
George Abraham ◽  
Vijay Patil ◽  
Amit Joshi ◽  
Nandini Menon ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Real World Data ◽  
World Data

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 Immune-related adverse events of immune checkpoint inhibitors: a brief review

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
G. Myers
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Health Care Professionals ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
T Cell Response ◽  
Proactive Management ◽  
Organ Systems

Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality.Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose–toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy.Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.

scholarly journals Thrombotic Complications Associated with Immune Checkpoint Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4606
Author(s):  
Tzu-Fei Wang ◽  
Alok A. Khorana ◽  
Marc Carrier
Keyword(s):  
Immune Checkpoint ◽  
Arterial Thrombosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Relevant Information ◽  
Anticancer Treatment ◽  
Thrombotic Complications ◽  
Associated Risk Factors ◽  
Cancer Associated Thrombosis

Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies. In this review, we synthesize data from available literature, provide relevant information for clinicians and potential future directions for research.

Sign in / Sign up

Export Citation Format

Share Document