Oncology & Haematology最新文献

{"title":"Zanubrutinib for the Treatment of B-cell Malignancies","authors":"A. Rosenthal, J. Muñoz","doi":"10.17925/ohr.2022.18.1.44","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.44","url":null,"abstract":"Selective Bruton's tyrosine kinase (BTK) inhibition is an important therapeutic approach for B-cell malignancies. Ibrutinib, a first-in-class, oral, irreversible BTK inhibitor, has a toxicity profile attributed to off-target inhibition of kinases structurally related to BTK. A highly potent and selective next-generation BTK inhibitor, zanubrutinib, was designed to address intolerance and toxicity concerns associated with ibrutinib. Zanubrutinib provides complete and sustained BTK occupancy in peripheral blood mononuclear cells and lymph nodes, with reduced toxicity compared with ibrutinib. Zanubrutinib received accelerated approval in the USA for patients with previously treated mantle cell lymphoma (2019) and relapsed/refractory (R/R) marginal zone lymphoma (2021) and was approved for Waldenström's macroglobulinaemia (WM) in 2021. Key clinical trials evaluating the efficacy and safety of zanubrutinib include the ASPEN study in patients with WM (ClinicalTrials.gov identifier: NCT03053440), the ALPINE study in patients with R/R chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL; ClinicalTrials.gov identifier: NCT03734016) and the SEQUOIA study in treatment-naïve patients with CLL/SLL with and without del(17p) mutation (ClinicalTrials.gov identifier: NCT03336333). The more selective BTK binding profile, high potency, favourable pharmacokinetic and pharmacodynamic profile, and minimal cardiovascular toxicity of zanubrutinib compared with ibrutinib suggest that zanubrutinib may be an important treatment option when prescribed in accordance with guidelines.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124587904","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":"COVID Coagulopathy and Thrombosis: A Systematic Review","authors":"R. Asrani, W. Bahou","doi":"10.17925/ohr.2022.18.1.78","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.78","url":null,"abstract":"Introduction: Since the onset of the SARS-CoV-2 pandemic, haematological laboratory abnormalities and thrombotic complications have been observed among infected patients. We aimed to highlight key pathophysiological mechanisms of COVID-19-associated coagulopathy and to summarize incidence rates of venous and arterial thrombotic events, comorbidities conferring risk, and current treatment guidelines including data from ongoing clinical trials. Methods: A systematic review was performed according to PRISMA recommendations of case–control studies, cohort studies, observational studies and randomized clinical trials (RCTs) published between 1 December 2019 and 30 September 2021 within PubMed and Web of Science. Inclusion criteria were English language, adult patients and at least one coagulation parameter described. Results: 2,554 records were screened, from which 59 studies were included. Abnormalities in several laboratory parameters were associated with worse clinical outcomes including elevations in prothrombin time, activated partial thromboplastin time, D-dimer, fibrinogen, von Willebrand factor antigen/activity and lupus anticoagulant antibodies. Rates of venous and arterial thromboembolism varied significantly among studies performed early in the pandemic and across different nations. Pathophysiological mechanisms included vascular endotheliopathy, increased inflammation and macrophage activation, neutrophil extracellular traps, antiphospholipid antibody production and obesity/adipose tissue signalling. Current recommendations for management of COVID coagulopathy from various societies include the use and dosing of systemic anticoagulation to prevent thrombotic sequelae in the outpatient, inpatient and critical care settings. The optimal anticoagulant dose for thromboprophylaxis in the inpatient and critical care settings is currently not well established. Conclusions: SARS-CoV-2 infection can cause a distinct form of coagulopathy, with thromboembolic complications leading to significant morbidity and mortality. The optimal treatment requires further refinement pending the results from key ongoing RCTs","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"75 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":"124052101","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 and Future Therapies for Marginal Zone Lymphoma","authors":"N. Chilakamarri, Karla Olmedo, E. Brem","doi":"10.17925/ohr.2022.18.1.40","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.40","url":null,"abstract":"Marginal zone lymphoma (MZL) is an indolent non-Hodgkin lymphoma with three subtypes: nodal, extranodal and splenic. Initial therapies can vary based on the subtype of MZL, location of disease and stage of disease. Treatment of MZL in the relapsed refractory (R/R) setting has evolved in recent years with the approvals of Bruton's tyrosine kinase inhibitors, phosphoinositide 3-kinase inhibitors and an immune modulatory drug, lenalidomide. Questions remain as to how best to use these agents to maximize efficacy and minimize toxicity. In this article, we focus on the management of MZL with currently available agents, particularly in the R/R setting. We also examine the therapies that may further change the treatment paradigm for MZL. Specifically, we discuss the available data for chimeric antigen receptor T-cell therapies and CD20–CD3 bispecific antibodies, and consider the limitations and potential benefits of these approaches.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"10 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":"126507975","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":"Trastuzumab Deruxtecan for the Treatment of HER2-positive Breast Cancer","authors":"T. Yamashita","doi":"10.17925/ohr.2023.19.1.6","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.6","url":null,"abstract":"Trastuzumab deruxtecan (T-DXd) is a new-generation anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate that has demonstrated good efficacy due to its stable linker, high drug–antibody ratio, and high bystander effect resulting from the efficient cell membrane permeability of its payload. The DESTINY-Breast01 trial showed a response rate of >60% in patients with HER2-positive advanced recurrent breast cancer who had received a median of six regimens of prior therapy. The DESTINY-Breast03 trial, which compared T-DXd with trastuzumab emtansine (T-DM1) in HER2-positive unresectable and/or metastatic breast cancer also showed very high efficacy. Although T-DXd is highly effective, it is associated with a greater incidence of interstitial pneumonia than conventional anti-HER2 agents such as T-DM1. HER2-positive breast cancer frequently develops brain metastases, the drug therapy for which has had extremely limited success. Recently, however, in a small number of trials, T-DXd has been reported to be effective against brain metastasis, by shrinking BM.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"47 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":"122235522","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":"Use of Circulating Tumour DNA to Assess Minimal Residual Disease in Gastrointestinal Cancers","authors":"Reetu Mukherji, Ali J Alqahtani, Harrison D. Winters, B. Weinberg","doi":"10.17925/ohr.2022.18.1.26","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.26","url":null,"abstract":"Despite our modern perioperative therapies, many patients with gastrointestinal cancer relapse after surgery. Novel strategies to identify and treat patients at high risk of relapse are needed to improve cancer outcomes. Circulating tumour DNA (ctDNA) is a promising, non-invasive biomarker with the potential to identify the earliest signs of cancer relapse. The presence of tumourspecific DNA in the blood in the absence of visualized tumour is suggestive of minimal residual disease and forebodes measurable relapse. Genomic sequencing techniques have advanced over the past few decades, and we have become better able to detect significantly low levels of DNA circulating in the blood from low-volume disease. Numerous studies using various technologies have established ctDNA as a powerful prognostic biomarker for relapse and survival in gastrointestinal cancers. ctDNA has the potential to risk-stratify patients in the postoperative, post-adjuvant and longitudinal settings for therapeutic escalation or de-escalation strategies. It may also capture early tumour dynamics in response to therapeutic intervention. As the multifaceted potential of ctDNA is attracting the attention of researchers, clinicians and patients, many questions remain regarding its use, interpretation and limitations. Here, we discuss the current understanding of ctDNA for minimal residual disease evaluation in gastrointestinal cancers and potential future directions.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"18 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":"115265934","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":"Pembrolizumab and Chemotherapy in Cervical Cancer: A New Standard of Care?","authors":"C. Lebreton, O. Saux, B. Mery, M. Bini, C. Romeo, I. Ray-Coquard","doi":"10.17925/ohr.2022.18.1.2","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.2","url":null,"abstract":"Cervical cancer (CC) still has a high incidence despite screening programmes and access to human papillomavirus (HPV) vaccination, with a poor prognosis in the advanced setting. Most cases of cervical carcinoma are related to HPV infection. The pathogen-induced nature of the disease, the involvement of genes regulating the immune response and the high grade of immune infiltration provide the rationale to evaluate anti-programmed death-(ligand)1 (PD-[L]1) immune checkpoint inhibitors in CC. This article reviews the promising outcomes of the KEYNOTE-826 phase III trial, which evaluates the addition of pembrolizumab to chemotherapy in patients with PD-L1-positive disease and recurrent, persistent or metastatic cancer of the cervix, leading to an improvement of progression-free survival and overall survival. We also aim to address some outstanding questions and discuss the next steps in immunotherapy for CC.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"7 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":"128561839","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":"Updates in the Management of Multiple Myeloma from the American Society of Hematology Meeting 2021","authors":"S. Vasudevan, Sravani Gundarlapalli, N. Thalambedu, Meera Mohan","doi":"10.17925/ohr.2022.18.1.53","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.1.53","url":null,"abstract":"Multiple myeloma (MM) remains largely an incurable disease with only a small percentage of patients achieving long-term remission. Here, we highlight some of the major studies on MM presented at the American Society of Hematology meeting in December 2021. Early results of the first ever population-based screening studies for precursor states of MM, iStopMM and PROMISE, were reported. These studies will inform on the risks and benefits of screening in MM and could lead to a paradigm shift towards screening and early therapy. In newly diagnosed MM, there were promising data on quadruple therapy with addition of a monoclonal antibody against the CD38 antigen to the existing backbone of lenalidomide, bortezomib and dexamethasone. T-cell–directed therapy including bispecific antibody and chimeric antigen receptor therapy demonstrated high clinical response, especially in triple-class refractory myeloma. We acknowledge that this review focuses on some exciting studies in both precursor and active MM and is not comprehensive by any means.","PeriodicalId":249239,"journal":{"name":"Oncology & Haematology","volume":"26 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":"116002916","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":"Pafolacianine: A Diagnostic Agent to Identify Lung Cancer Lesions in Adults with Known or Suspected Lung Cancer","authors":"L. Martin","doi":"10.17925/ohr.2023.19.1.2","DOIUrl":"https://doi.org/10.17925/ohr.2023.19.1.2","url":null,"abstract":"<p />","PeriodicalId":249239,"journal":{"name":"Oncology &amp; Haematology","volume":"17 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":"114671476","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":"ATLAS: Risk-adapted Triplet Maintenance with Carfilzomib, Lenalidomide and Dexamethasone – Still Shrugging?","authors":"Joseph K Franz, S. Lonial","doi":"10.17925/ohr.2022.18.2.96","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.2.96","url":null,"abstract":"ATLAS (ClinicalTrials.gov Identifier: NCT02659293) is a randomized phase III clinical trial comparing intensified carfilzomib, lenalidomide and dexamethasone (KRd) maintenance to standard-of-care, single-agent lenalidomide. The recently reported primary analysis showed a progression-free survival benefit for KRd. Whilst the study met its primary endpoint, closer analysis of its design and results is necessary before this intensified maintenance strategy can be adopted in clinical practice.","PeriodicalId":249239,"journal":{"name":"Oncology &amp; Haematology","volume":"13 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":"122273581","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":"Is Triple Therapy the New Standard for Metastatic Hormone-sensitive Prostate Cancer?","authors":"J. Hack, S. Crabb","doi":"10.17925/ohr.2022.18.2.120","DOIUrl":"https://doi.org/10.17925/ohr.2022.18.2.120","url":null,"abstract":"The treatment of metastatic hormone-sensitive prostate cancer has rapidly changed over the last decade. Currently, standard of care (SOC) options for first-line treatment are androgen deprivation therapy (ADT) in combination with either docetaxel chemotherapy or an androgen receptor pathway inhibitor such as abiraterone, enzalutamide or apalutamide. Recent results from both the PEACE-1 and ARASENS trials show an overall survival and progression-free survival benefit from the addition of an androgen-receptor pathway inhibitor for patients in whom the SOC option of ADT plus docetaxel has been chosen in de novo metastatic hormone-sensitive prostate cancer, with a more pronounced benefit in those with high-volume metastatic disease. However, many clinicians now preferentially use ADT plus an androgen-receptor pathway inhibitor as SOC first-line treatment, and no prospective trial has addressed whether there is a benefit from the addition of docetaxel to this version of SOC combination therapy. The benefit of triplet combination therapy in those with recurrent or low-volume metastatic disease is less clear and longer follow-up is required before conclusions can be drawn about these patient groups.","PeriodicalId":249239,"journal":{"name":"Oncology &amp; 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":"134051253","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}