E. Golden, S. Ingram, H. Schade, J. Matous, T. Gregory
{"title":"Novel Therapies in BCMA-exposed Relapsed/Refractory Multiple Myeloma: The Anti-BCMA Therapy-refractory Patient","authors":"E. Golden, S. Ingram, H. Schade, J. Matous, T. Gregory","doi":"10.17925/ohr.2022.18.1.59","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.59","url":null,"abstract":"Multiple myeloma (MM) is a haematologic malignancy resulting from the malignant overgrowth of monoclonal plasma cells in the bone marrow. Nearly 35,000 new cases are expected in the USA each year. In the last two decades there have been many clinical advances with the approvals of many new drugs and their combinations, which have improved survival statistics. Despite this, MM remains incurable, and patients with relapsed/refractory MM remain vulnerable. The development of chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results utilizing several target antigens; of note, B-cell maturation antigen (BCMA) is most prominent, due to its universal expression on the surface of malignant plasma cells. While anti-BCMA CAR-T therapies are inspiring, most patients eventually relapse and require further treatment. With these patients progressing through standard-of-care therapies, and more recently through novel anti-BCMA CAR-T therapies, we are faced with exploring novel treatment regimens to challenge their diseases. In this review, we discuss the different mechanisms of resistance to anti-BCMA therapies, effective retreatment with anti-BCMA-targeted therapies in MM, and advances in therapies utilizing other novel targets for patients who have progressed through anti-BCMA treatment.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129447805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Evolving Therapeutic Landscape and Role of Enfortumab Vedotin in Advanced Urothelial Carcinoma: A Systematic Review","authors":"R. Talukder, D. Makrakis, P. Grivas, A. Khaki","doi":"10.17925/ohr.2023.19.1.27","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.27","url":null,"abstract":"The therapeutic landscape in advanced urothelial carcinoma (aUC) has been rapidly evolving over the last 6 years. Enfortumab vedotin (EV) is an antibody–drug conjugate that targets Nectin-4, which is widely expressed in UC. EV is approved by the US Food and Drug Administration for patients with aUC refractory to prior therapy. EV is now being investigated in combination with other therapeutic agents, such as immune checkpoint inhibitors, both in first-line and refractory settings in aUC as well as earlier therapy settings. In this review, we summarized the role of EV in the rapidly evolving therapeutic landscape of aUC.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"436 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125842713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current State of Targeted Therapy and Immunotherapy in Advanced Gastric and Gastro-oesophageal Cancers","authors":"Ali J Alqahtani, Chao Yin, J. Marshall, M. Noel","doi":"10.17925/ohr.2022.18.1.16","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.16","url":null,"abstract":"Gastro-oesophageal cancer (GEC) is one of the world's deadliest forms of cancer. The conventional multi-modality approach to oesophageal cancer includes surgical resection, radiation and chemotherapy. However, due to the often-advanced nature of GEC on diagnosis, the limited efficacy of conventional therapies and the severe side effects of conventional treatments, the reported results are underwhelming. In the pursuit of better systemic therapies, targeted agents have played a vital role in GEC management. Said therapies essentially inhibit pathways such as the human epidermal growth factor receptor-2, vascular endothelial growth factor, epidermal growth factor receptor and programmed death receptor 1/programmed death-ligand 1 (i.e. immunotherapies). This review outlines a clinical summary of the most recent breakthroughs in targeted therapy for GEC and their associated clinical data, including efficacy and safety profiles.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127831825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nivolumab Combination Therapy for the Treatment of Unresectable Advanced or Metastatic Oesophageal Squamous Cell Carcinoma","authors":"Y. Yoshinami, S. Yamamoto, Ken Kato","doi":"10.17925/ohr.2023.19.1.17","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.17","url":null,"abstract":"Oesophageal cancer (OC) is the seventh most common malignancy worldwide, and there are few effective treatment options for advanced OC. Fluoropyrimidine and platinum-based chemotherapy has been the standard first-line treatment for advanced oesophageal squamous cell carcinoma (OSCC) but the survival outcomes are poor. Therefore, there is a need to develop new, more effective drugs. Immune checkpoint inhibitors (ICIs) have emerged as a new standard treatment for several malignancies. Nivolumab, a human monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein-1, has been developed for the treatment of advanced OSCC. Nivolumab monotherapy demonstrated clinical efficacy and safety in patients with OSCC in the ATTRACTION-3 trial, and was approved by the United States Food and Drug Administration as later-line treatment for patients with previously treated OSCC, regardless of programmed cell death protein-1 ligand expression status. Recently, the CheckMate 648 trial demonstrated the efficacy and safety of both an ICI in combination with chemotherapy, and a dual ICI combination, as first-line treatment for patients with advanced OSCC. This review discusses the current status of nivolumab combination therapy for patients with advanced OSCC, and future perspectives.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127047944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gianfranco Bittar, Diana De Oliveira-Gomes, G. Rivero
{"title":"Advances and Future Goals in Acute Myeloid Leukaemia Therapy","authors":"Gianfranco Bittar, Diana De Oliveira-Gomes, G. Rivero","doi":"10.17925/ohr.2022.18.2.130","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.2.130","url":null,"abstract":"The treatment of acute myeloid leukaemia (AML) remains challenging, given the disease's heterogeneous genomics, epigenetics and immunology. Although novel drugs are rapidly being developed, the outcomes of patients with AML remain suboptimal, especially among individuals older than 75 years and those with primary relapsed/refractory disease. While molecular characterization can inform the use of targeted therapies, several limitations, including low response rates and short durations of remission when targeted agents are used as monotherapies, restrict the efficacy of this strategy. It is likely that combining targeted agents with either chemotherapy or hypomethylating agents will help to advance the field. Here, we review current cytogenetic and genomic European LeukemiaNet risk-stratification models for AML. We present the cases of three patients with AML that illustrate the therapeutic recommendations for patients in specific genomic subgroups, emphasizing recent results with a hypomethylating agent plus B-cell lymphoma 2 inhibitor therapy in elderly patients. Finally, we summarize data from clinical trials that promise to improve AML therapy.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124353624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Utility of Human Papillomavirus Circulating Tumour DNA in Human Papillomavirus-positive Head and Neck Squamous Cell Carcinomas","authors":"Karen M Yun, E. Cohen","doi":"10.17925/ohr.2022.18.2.125","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.2.125","url":null,"abstract":"Human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCCs) are a subtype of virally driven tumours with favourable responses to definitive therapy. However, disease relapse or progression is clinically challenging due to limited effective treatment options. Circulating tumour DNA (ctDNA) technology has emerged in the past decade, and it remains an active area of research in head and neck cancers. A variety of assays for the analysis of HPV ctDNA in patients with HPV-positive HNSCC have been developed and studied, though standardization in HPV ctDNA testing has yet to be established. Studies show promise in HPV ctDNA as a prognostic biomarker and predictor of treatment response and risk for recurrence. Growing evidence suggests that absolute HPV ctDNA quantification, as well as dynamic changes in HPV ctDNA concentration, can potentially inform outcomes and guide decisions about therapy. The aim of this article is to review the clinical utility of HPV ctDNA as a biomarker in HNSCC.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"155 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123308091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retifanlimab and Other Immune Checkpoint Inhibitors for Squamous Cell Anal Carcinoma","authors":"J. Mencel, S. Rao","doi":"10.17925/ohr.2023.19.1.41","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.41","url":null,"abstract":"Metastatic squamous cell anal carcinoma (SCAC) accounts for almost 500 deaths per year in the UK. The optimal first-line treatment for metastatic SCAC consists of combination chemotherapy, which provides only modest benefit with a short duration of response. Currently, there is no established second-line treatment for chemorefractory disease. Retifanlimab (a programmed cell death protein 1 inhibitor) has shown promise in patients with refractory, metastatic SCAC based on the POD1UM-202 study, and has potential in the first-line setting in combination with chemotherapy. This article will review the current treatment paradigms for SCAC, including the future use of immune checkpoint inhibitors, with a focus on retifanlimab in the treatment of SCAC.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125544223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in Targeted Therapy for Patients with Neuroendocrine Tumours","authors":"Vatsala Katiyar, Satya Das","doi":"10.17925/ohr.2022.18.1.66","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.66","url":null,"abstract":"Neuroendocrine neoplasms are heterogenous tumours with diverse biological behaviour. Well-differentiated neuroendocrine tumours comprise the vast majority of these malignancies. Though a subset of patients may possess indolent disease, which can be observed, most patients require systemic therapy at some point. The treatment armamentarium for patients with metastatic or advanced well-differentiated neuroendocrine tumours has expanded significantly over recent years, with multiple regulatory approvals for systemic therapies. Though peptide receptor radionuclide therapy has been a major addition to this armamentarium, several targeted therapies have also been successfully developed. Herein, we discuss the approved targeted therapies sunitinib and everolimus and highlight the clinical experience with targeted therapies in development. We focus largely on novel receptor tyrosine kinases targeting vascular endothelial growth factor, inhibitors of cell-cycle drivers, metabolic-pathway inhibitors and chemotherapy, and immune-modulating agents targeting the somatostatin receptor.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121397156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sutimlimab for the Treatment of Cold Agglutinin Disease","authors":"I. Weitz","doi":"10.17925/ohr.2023.19.1.35","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.35","url":null,"abstract":"Cold agglutinin disease is a very rare haemolytic anaemia characterized by antibody-mediated haemolysis, complement activation, thrombosis and poor quality of life. In recent years, our understanding of the complement system and its role in disease has increased dramatically. However, because there is an increased risk of infection with inhibiting complement at the complement 5 and complement 3 levels, blocking the classical complement pathway is being explored instead as a way to strategically inhibit the complement system while minimizing the infection risks. Sutimlimab is a humanized immunoglobulin G4 antibody developed to inhibit the classical complement pathway. Its role and efficacy in treating patients with cold agglutinin disease will be the focus of this paper.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"93 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125209378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Durvalumab: A PD-L1 Blocking Antibody for the Treatment of Adult Patients with Locally Advanced or Metastatic Biliary Tract Cancer","authors":"A. Mahipal, M. Palmer, J. Gile, R. Kim","doi":"10.17925/ohr.2023.19.1.22","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.22","url":null,"abstract":"Biliary tract cancers (BTCs), comprising intrahepatic, hilar and extrahepatic cholangiocarcinoma and gallbladder cancers, are associated with poor prognoses. The majority of patients present with advanced-stage disease, and systemic treatment remains the mainstay of treatment. Recently, multiple targeted therapies have been approved by the US Food and Drug Administration (FDA), including pemigatinib, infigratinib, futibatinib and ivosidenib for patients whose disease has progressed on first-line systemic therapy. However, there has been no improvement on the first-line systemic therapeutic regimen of gemcitabine and cisplatin chemotherapy in more than a decade. Recently, durvalumab in addition to gemcitabine plus cisplatin was approved by the FDA as a first-line treatment option for patients with advanced BTC based on the TOPAZ-1 trial. The TOPAZ-1 trial was a phase III double-blind, placebo-controlled trial that enrolled 685 patients into a durvalumab plus gemcitabine plus cisplatin arm or a gemcitabine plus cisplatin arm. The trial demonstrated that the addition of durvalumab to standard-of-care chemotherapy was associated with improvement in median overall survival (12.8 versus 11.5 months), progression-free survival (7.2 versus 5.7 months) and response rates (27% versus 19%). The incidence and severity of adverse events were similar in both groups. Durvalumab in addition to gemcitabine plus cisplatin has become the new standard-of-care treatment for patients with advanced BTCs. This article reviews the immunotherapeutic options for patients with BTCs, describes the studies that led to the TOPAZ-1 trial, and summarizes key areas of research that are necessary to inform future drug development and improve patient outcomes.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"46 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120985857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}