Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"Impact of obinutuzumab alone and in combination for follicular lymphoma","authors":"M. Sarraf Yazdy, B. Cheson","doi":"10.2147/BLCTT.S114173","DOIUrl":"https://doi.org/10.2147/BLCTT.S114173","url":null,"abstract":"Although rituximab-based chemoimmunotherapy prolongs the survival of patients with follicular lymphoma (FL), this disease is considered incurable in most patients. Thus, new therapies are needed not only for those in the relapsed/refractory setting, but also for initial treatment. Obinutuzumab (G, GA101) is a third-generation, fully humanized type II glycoengineered, anti-CD20 monoclonal antibody that results in increased direct cell death and antibody-dependent, cell-mediated cytotoxicity/phagocytosis compared to rituximab. Obinutuzumab has significant antitumor activity when used alone or in combinations in untreated or relapsed refractory FL patients. Studies have demonstrated its ability to prolong progression-free survival and, in some cases, overall survival, and to eliminate minimal residual disease. Several ongoing trials are investigating combinations with chemotherapy, immunomodulators, targeted drugs, and immunotherapy agents. G is generally well tolerated, with associated adverse effects including infusion-related reactions, neutropenia, thrombocytopenia, and reactivation of hepatitis B virus. Future studies with this antibody should focus on identifying predictive markers and developing chemotherapy-free combinations that will improve the outcome of patients with FL.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"1 1","pages":"73 - 83"},"PeriodicalIF":2.8,"publicationDate":"2017-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87358642","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 carfilzomib in second-line therapy and beyond for relapsed multiple myeloma","authors":"D. Bhutani, J. Zonder","doi":"10.2147/BLCTT.S82444","DOIUrl":"https://doi.org/10.2147/BLCTT.S82444","url":null,"abstract":"The development of proteasome inhibitors has been a major advance in therapy of multiple myeloma, accounting, in part, for the significant increase in the survival of patients diagnosed with this disease. Bortezomib was the first proteasome inhibitor to be approved for the therapy of multiple myeloma. Carfilzomib is a second-generation proteasome inhibitor with irreversible binding to proteasome and less off-target toxicity. The drug has been approved for use in relapsed/refractory multiple myeloma. In this article, we review the use of carfilzomib as second-line therapy in multiple myeloma. We also review the current standards of care for relapsed/refractory multiple myeloma, with particular focus on the use of carfilzomib in advanced disease.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"33 1","pages":"53 - 60"},"PeriodicalIF":2.8,"publicationDate":"2017-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76517961","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 potential of midostaurin in advanced systemic mastocytosis","authors":"M. Chandesris, G. Damaj, O. Lortholary, O. Hermine","doi":"10.2147/BLCTT.S87186","DOIUrl":"https://doi.org/10.2147/BLCTT.S87186","url":null,"abstract":"Advanced (Ad) systemic mastocytoses (SM) include aggressive SM (ASM) and mast cell leukemia (MCL) with or without an associated clonal hematological non-mast cell lineage disease (AHNMD). They are rare (<15%) but are associated with a poor prognosis due to rapid organ dysfunction. To date, responses to high-dose chemotherapy, cladribine, and imatinib were revealed to be suboptimal with a median survival time of 24 months. Midostaurin is a potent multikinase inhibitor including the most frequent KIT D816V mutation (>80%). We herein present a review of the most recent data of the use of midostaurin in AdSM. First, a multicenter Phase II study (CPKC412D2213) revealed an unprecedented overall response rate (ORR) of 69% regardless of KIT mutational status, with 38% of major response (MR) among 26 AdSM patients treated with midostaurin alone 200 mg daily. Second, a sponsor-initiated, multicenter, single-arm open Phase II study (CPKC412D2201) confirmed a high and durable ORR of 60% including 45% of MR among 89 AdSM patients. Finally, a French compassionate use program managed by the French Reference Centre for Mastocytosis allowed the treatment of almost a hundred AdSM patients to date in France since the CPKC412D2201 study closure. The outcome of the first 28 treated patients under cover of this on-going procedure revealed an ORR of 71% including 57% of MR. Most importantly, survival analysis revealed in comparison to a historical control cohort of AdSM patients who did not receive midostaurin a twofold lower risk of death (p=0.02) in midostaurin-treated patients. Side effects revealed were acceptable and manageable (mostly digestive). Midostaurin appears to be an effective and safe treatment of AdSM. However, its effect on the course of the AHNMD is less clear. For the future, combined therapy (hypomethylating agents, cladribine, mammalian target of rapamycin inhibitors, chemotherapy, and allogeneic bone marrow transplantation) may further improve long-term survival, particularly that of MCL and AdSM patients with AHNMD.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"21 1","pages":"25 - 35"},"PeriodicalIF":2.8,"publicationDate":"2017-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82955371","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":"Uptake of lymphoma-derived exosomes by peripheral blood leukocytes","authors":"Heather R. Ferguson Bennit, Amber Gonda, L. Oppegard, David P Chi, Salma Khan, N. Wall","doi":"10.2147/BLCTT.S130826","DOIUrl":"https://doi.org/10.2147/BLCTT.S130826","url":null,"abstract":"Exosomes are nanosized lipid vesicles secreted into blood and other body fluids and serve as vehicles for intercellular communication. Despite being an important component of the tumor microenvironment (TME), exosomal targeting and uptake into recipient cells are still not fully understood. Few studies have looked at lymphoma exosomes and their interactions with circulating blood cells. In this study, we examine the exosomal uptake distribution among peripheral blood leukocytes (PBLs) using vesicles derived from a diffuse large B cell lymphoma cell line, WSU-DLCL2. Lymphoma cells survive, proliferate, and are protected from the cytotoxic effects of chemotherapeutic agents by soluble factors or by direct contact with inflammatory and stromal cells within the TME. In an attempt to close the gap in knowledge concerning lymphoma TME immunosuppression, we have treated normal human PBLs with PKH67-labeled lymphoma exosomes and monitored the uptake by measuring fluorescence at different time points using flow cytometry and fluorescent microscopy. Our results show that of the four populations examined, B cells and monocytes demonstrated uptake of PKH67-labeled exosomes, while T cells and NK cells displayed significantly less uptake.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"22 1","pages":"9 - 23"},"PeriodicalIF":2.8,"publicationDate":"2017-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76483237","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":"Harnessing the immune system through programmed death-1 blockade in the management of Hodgkin lymphoma.","authors":"Melody B Oncale, Hossein Maymani, Loretta J Nastoupil","doi":"10.2147/BLCTT.S110665","DOIUrl":"10.2147/BLCTT.S110665","url":null,"abstract":"<p><p>Immunotherapy is a rapidly evolving therapeutic option in the treatment of lymphoma. Neoplastic cells evade immune recognition through the programmed death (PD)-1/PD-ligand immune checkpoint pathway. Several novel agents have been developed to restore the immune system's ability to recognize and destroy cancer cells. Nivolumab and pembrolizumab are two anti-PD-1 antibodies that have demonstrated success in the treatment of refractory Hodgkin lymphoma. Harnessing the immune system's ability to target neoplastic cells, ideally without the use of cytotoxic chemotherapeutic agents, is one way in which these novel agents are changing the therapeutic landscape in the treatment of lymphomas. Here, we review the emerging data regarding checkpoint inhibitors in the management of Hodgkin lymphoma, the unique adverse effects encountered with the use of these agents, and a practical approach to the management of these adverse effects. Additionally, we discuss upcoming trials that will further assess the promising future developments of checkpoint inhibition in the treatment of not only Hodgkin lymphoma but also other B cell lymphomas and myeloma. These agents offer immense promise of a future where many lymphomas can be treated without the toxic effects of chemotherapeutic agents.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"7 ","pages":"1-7"},"PeriodicalIF":3.9,"publicationDate":"2017-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/6e/blctt-7-001.PMC6467338.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215412","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":"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":"7 ","pages":"37-52"},"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":"27 1","pages":"49 - 58"},"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":"6 ","pages":"37-47"},"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":"6 ","pages":"21-35"},"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":"08 1","pages":"7 - 19"},"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}