Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"Advances in the pathophysiology and treatment of relapsed/refractory Hodgkin's lymphoma with an emphasis on targeted therapies and transplantation strategies.","authors":"Theodoros Karantanos,&nbsp;Ioannis Politikos,&nbsp;Vassiliki A Boussiotis","doi":"10.2147/BLCTT.S105458","DOIUrl":"https://doi.org/10.2147/BLCTT.S105458","url":null,"abstract":"<p><p>Hodgkin's lymphoma (HL) is highly curable with first-line therapy. However, a minority of patients present with refractory disease or experience relapse after completion of frontline treatment. These patients are treated with salvage chemotherapy followed by autologous stem cell transplantation (ASCT), which remains the standard of care with curative potential for refractory or relapsed HL. Nevertheless, a significant percentage of such patients will progress after ASCT, and allogeneic hematopoietic stem cell transplantation remains the only curative approach in that setting. Recent advances in the pathophysiology of refractory or relapsed HL have provided the rationale for the development of novel targeted therapies with potent anti-HL activity and favorable toxicity profile, in contrast to cytotoxic chemotherapy. Brentuximab vedotin and programmed cell death-1-based immunotherapy have proven efficacy in the management of refractory or relapsed HL, whereas several other agents have shown promise in early clinical trials. Several of these agents are being incorporated with transplantation strategies in order to improve the outcomes of refractory or relapsed HL. In this review we summarize the current knowledge regarding the mechanisms responsible for the development of refractory/relapsed HL and the outcomes with current treatment strategies, with an emphasis on targeted therapies and hematopoietic stem cell transplantation.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S105458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35165786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Waldenström macroglobulinemia: biology, genetics, and therapy","authors":"J. Paludo, S. Ansell","doi":"10.2147/BLCTT.S84157","DOIUrl":"https://doi.org/10.2147/BLCTT.S84157","url":null,"abstract":"Waldenström macroglobulinemia (WM) is a distinct clinicopathologic entity characterized by the presence of a lymphoplasmacytic lymphoma, a non-Hodgkin lymphoma, and IgM monoclonal gammopathy. WM is an indolent, uncommon malignancy mostly affecting the elderly. Patient outcomes have modestly improved since the introduction of rituximab to conventional cytotoxic chemotherapy more than 20 years ago. However, the pivotal discovery of the somatic MYD88 L265P mutation, harbored by most patients with WM, and the somatic CXCR4 WHIM mutations, similar to germline CXCR4 mutations seen in the warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis (WHIM) syndrome, present in approximately one-third of patients with WM, has fundamentally changed our understanding of this disease and expanded the potential therapeutic targets. Within this new paradigm, ibrutinib emerged as a promising new drug. Ibrutinib targets Bruton’s tyrosine kinase, a downstream protein in the B-cell receptor pathway that is overactivated by the MYD88 L265P mutation. A seminal Phase II trial of ibrutinib in previously treated WM patients showed impressive response rates and confirmed the effects of MYD88 L265P and CXCR4 WHIM mutations in response to therapy. Ibrutinib is the first and only US Food and Drug Administration–approved drug specifically for the treatment of WM. However, before ibrutinib can be established as the standard of care for WM, long-term data regarding efficacy and safety are required. Further research to address ibrutinib resistance and cost-effectiveness is also imperative before ibrutinib can gain widespread acceptance. This review will cover the present pathophysiologic understanding of WM in light of the recent MYD88 and CXCR4 discovery, as well as current and emergent treatment regimens with focus on ibrutinib.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2016-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86627474","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":"Managing treatment-related peripheral neuropathy in patients with multiple myeloma.","authors":"Sara Grammatico, Laura Cesini, Maria Teresa Petrucci","doi":"10.2147/BLCTT.S91251","DOIUrl":"10.2147/BLCTT.S91251","url":null,"abstract":"<p><p>Peripheral neuropathy is one of the most important complications of multiple myeloma treatment. Neurological damage can be observed at the onset of the disease, due to the effect of monoclonal protein or radicular compression, but more often is treatment related. Vinca alkaloids in the past era, and more recently, thalidomide and bortezomib are mainly responsible. Degeneration of dorsal root ganglion is common, prevalently related to angiogenesis inhibition and cytokine modulation in the case of thalidomide and inhibition of the ubiquitin proteasome system in the case of bortezomib. Sensory neuropathy and neuropathic pain are more common; motor neuropathy and autonomic damage are less frequently observed. Neurotoxicity often affects patient's quality of life and requires dose modification or withdrawal of therapy, with a possible effect on the overall response. A prompt recognition of predisposing factors (such as diabetes mellitus, alcohol abuse, vitamin deficiencies, or viral infections) and appearance of signs and symptoms, through a periodic neurological assessment with appropriate scales, is extremely important. Effective management of treatment at the emergence of peripheral neuropathy can minimize the incidence and severity of this complication and preserve therapeutic efficacy. Dose adjustment could be necessary during treatment; moreover, gabapentin or pregabalin, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, carbamazepine, and opioid-type analgesics are suggested according to the pain severity. Some authors reported that patients who develop peripheral neuropathy during their multiple myeloma treatments presented a particular gene expression profile; therefore, future studies could be helpful for a better understanding of possible biological pathways underlying neurotoxicity.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2016-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/eb/6a/blctt-6-037.PMC6467335.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment and monitoring of patients receiving chemotherapy for multiple myeloma: strategies to improve outcomes.","authors":"Beth Faiman, Jason Valent","doi":"10.2147/BLCTT.S90764","DOIUrl":"10.2147/BLCTT.S90764","url":null,"abstract":"<p><p>Improved understanding as to the biology of multiple myeloma (MM) and the bone marrow microenvironment has led to the development of new drugs to treat MM. This explosion of new and highly effective drugs has led to dramatic advances in the management of MM and underscores the need for supportive care. Impressive and deep response rates to chemotherapy, monoclonal antibodies, and small molecule drugs provide hope of a cure or prolonged remission for the majority of individuals. For most patients, long-term, continuous therapy is often required to suppress the malignant plasma cell clone, thus requiring clinicians to become more astute in assessment, monitoring, and intervention of side effects as well as monitoring response to therapy. Appropriate diagnosis and monitoring strategies are essential to ensure that patients receive the appropriate chemotherapy and supportive therapy at relapse, and that side effects are appropriately managed to allow for continued therapy and adherence to the regimen. Multiple drugs with complex regimens are currently available with varying side effect profiles. Knowledge of the drugs used to treat MM and the common adverse events will allow for preventative strategies to mitigate adverse events and prompt intervention. The purpose of this paper is to review updates in the diagnosis and management of MM, and to provide strategies for assessment and monitoring of patients receiving chemotherapy for MM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2016-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/d0/blctt-6-021.PMC6467334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ruxolitinib: a targeted treatment option for patients with polycythemia vera","authors":"K. Vaddi, S. Verstovsek, J. Kiladjian","doi":"10.2147/BLCTT.S101185","DOIUrl":"https://doi.org/10.2147/BLCTT.S101185","url":null,"abstract":"Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis and the presence of Janus kinase (JAK) 2V617F or similar mutations. This review summarizes the pathophysiology of PV, the challenges associated with traditional treatment options, and the scientific rationale and supportive clinical evidence for targeted therapy with ruxolitinib. Accumulating evidence indicates that activating mutations in JAK2 drive the PV disease state. Traditional PV treatment strategies, including aspirin, phlebotomy, and cytoreductive agents such as hydroxyurea, provide clinical benefits for some but not all patients and may not adequately treat PV-related symptoms. Furthermore, traditional treatment approaches are associated with potential side effects that may limit their usage and lead some patients to discontinue the treatment. Ruxolitinib is an orally available small-molecule tyrosine kinase inhibitor that is a potent and selective inhibitor of JAK1/JAK2. Ruxolitinib is approved in the US for patients with PV with an inadequate response or intolerance to hydroxyurea and in Europe for adults with PV who are resistant to or intolerant of hydroxyurea. In the Phase III RESPONSE registration trial, ruxolitinib was superior to the best available therapy in patients with PV who were resistant to or intolerant of hydroxyurea in controlling hematocrit levels, reducing spleen volume, and improving PV-related symptoms and quality-of-life measures. The most common nonhematologic adverse events in ruxolitinib-treated patients were headache, diarrhea, pruritus, and fatigue in the RESPONSE trial; hematologic adverse events were primarily grade 1 or 2. In the Phase IIIb nonregistration RELIEF trial, there were nonsignificant trends toward an improved symptom control in patients with PV on a stable hydroxyurea dose who were generally well controlled but reported disease-associated symptoms and switched to ruxolitinib vs those who continued hydroxyurea therapy. Updated treatment guidelines will be important for educating physicians about the role of ruxolitinib in the treatment of patients with PV.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2016-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79820450","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":"Idelalisib therapy of indolent B-cell malignancies: chronic lymphocytic leukemia and small lymphocytic or follicular lymphomas.","authors":"Yazan F Madanat,&nbsp;Mitchell R Smith,&nbsp;Alexandru Almasan,&nbsp;Brian T Hill","doi":"10.2147/BLCTT.S73530","DOIUrl":"https://doi.org/10.2147/BLCTT.S73530","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma are indolent B-cell lymphoproliferative disorders that mainly affect an older population. Although the majority of patients in need of treatment derive significant benefit from conventional chemotherapeutic agents as well as monoclonal antibodies, less toxic and more effective treatments are needed. Novel agents that inhibit the B-cell receptor signaling pathway have shown promising outcomes in these disorders. Idelalisib is a potent selective oral inhibitor of phosphatidylinositol 3-kinase delta and has shown significant clinical activity in B-cell malignancies. In this review, we summarize the clinical trial data using idelalisib as monotherapy or in combination with rituximab for the treatment of relapsed/refractory disease. The adverse effect profile includes autoimmune disorders such as transaminitis, colitis, and pneumonitis. Given the efficacy and manageable toxicity profile of idelalisib, it is being increasingly incorporated into the management of indolent B-cell malignancies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S73530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34633292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profile of elotuzumab and its potential in the treatment of multiple myeloma.","authors":"Yi-Chang Liu,&nbsp;Susann Szmania,&nbsp;Frits van Rhee","doi":"10.2147/BLCTT.S49780","DOIUrl":"https://doi.org/10.2147/BLCTT.S49780","url":null,"abstract":"<p><p>Although the introduction of novel drugs has improved outcome significantly in multiple myeloma (MM), many patients still eventually relapse. Monoclonal antibodies (mAbs) targeting MM-related antigens can complement currently available therapies. CS1 (also known as CD2 subunit 1, SLAMF7, CD319, and CRACC), a cell surface glycoprotein receptor that is a member of the signaling lymphocytic activation molecule (SLAM) family, is highly and nearly uniformly expressed in myeloma cells at the gene and protein level, but not expressed in other tissues, including hematopoietic stem cells, making CS1 a compelling target for the design of immunotherapies directed at MM. Elotuzumab (formerly HuLuc63), which is a humanized IgG1 mAb recognizing the extracellular region of human CS1, has been shown to be effective in preclinical and early stage clinical investigations, and its efficacy and safety will be further validated in ongoing Phase III trials. Integration of elotuzumab into multidrug therapeutic paradigms seems logical, as elotuzumab is more effective when combined with other agents, such as immunomodulatory drugs or proteasome inhibitors. The functional role of CS1 in MM pathogenesis and the consequences of elotuzumab on normal immune cells should be further investigated. Identification of potential biomarkers and exploration of resistance mechanisms are important issues for elotuzumab-based therapies, as is determining the best clinical placement of elotuzumab, not only in the relapsed/refractory setting but also in upfront therapy for high-risk frank MM, smoldering MM at high-risk of progression, and in maintenance regimens. This review will cover the biological characteristics of CS1 in normal immune cells and MM cells, the efficacy profile and mechanisms of action of elotuzumab from preclinical and clinical investigations, and its potential impact on the treatment of MM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S49780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33331147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Strategies for Patients with Diffuse Large B-Cell Lymphoma: Past, Present, and Future.","authors":"Rajni Sinha,&nbsp;Loretta Nastoupil,&nbsp;Christopher R Flowers","doi":"10.2147/BLCTT.S18701","DOIUrl":"10.2147/BLCTT.S18701","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring lymphoma in the Western world. DLBCL is a clinically, biologically, and pathologically heterogeneous entity with biologically distinct subtypes that have different expected treatment outcomes. The addition of rituximab to combination chemotherapy has improved outcomes for all patients with DLBCL and can produce cure for many individuals. Relapsed DLBCL is generally managed with salvage chemo-immunotherapy followed by high dose therapy and autologous stem cell transplantation which can cure additional patients. However, outcomes for patients who relapse early after upfront rituximab and chemotherapy have a poorer prognosis. Novel therapies and strategies are desperately needed for these patients and several emerging treatments hold promise for improving DLBCL treatment outcomes in the future.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2012-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S18701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40227396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}