Pub Date : 2020-09-30eCollection Date: 2020-09-01DOI: 10.21037/aol-20-20
Jennifer K Lue, Owen A O'Connor, Francesco Bertoni
Marginal zone lymphoma (MZL) represents a group of three distinct though overlapping lymphoid malignancies that includes extranodal, nodal and splenic marginal lymphoma. MZL patients usually present an indolent clinical course, although the disease remains largely incurable, save early stage disease that might be irradiated. Therapeutic advances have been limited due to the small patient population, and have largely been adapted from other indolent lymphomas. Here, we discuss the numerous targets and pathways which may offer the prospect of directly inhibiting the mechanisms identified promoting and sustaining marginal zone lymphomagenesis. In particular, we focus on the agents that may have at least a theoretical application in the disease. Various dysregulated pathways converge to produce an overarching stimulation of nuclear factor κB (NF-κB) and the MYD88-IRAK4 axis, which can be thus leveraged or targeting B-cell receptor signaling through BTK inhibitors (such as ibrutinib, zanubrutinib, acalabrutinib) and PI3K inhibitors (such as idelalisib, copanlisib, duvelisib umbralisib) or via more novel agents in development such as MALT1 inhibitors, SMAC mimetics, NIK inhibitors, IRAK4 or MYD88 inhibitors. NOTCH signaling is also crucial for marginal zone cells, but no clinical data are available with NOTCH inhibitors such as the γ-secretase inhibitor PF-03084014 or the NICD inhibitor CB-103. The hypermethylation phenotype, the overexpression of the PRC2-complex or the presence of TET2 mutations reported in MZL subsets make epigenetic agents (demethylating agents, EZH2 inhibitors, HDAC inhibitors) also potential therapeutic tools for MZL patients.
{"title":"Targeting pathogenic mechanisms in marginal zone lymphoma: from concepts and beyond.","authors":"Jennifer K Lue, Owen A O'Connor, Francesco Bertoni","doi":"10.21037/aol-20-20","DOIUrl":"10.21037/aol-20-20","url":null,"abstract":"<p><p>Marginal zone lymphoma (MZL) represents a group of three distinct though overlapping lymphoid malignancies that includes extranodal, nodal and splenic marginal lymphoma. MZL patients usually present an indolent clinical course, although the disease remains largely incurable, save early stage disease that might be irradiated. Therapeutic advances have been limited due to the small patient population, and have largely been adapted from other indolent lymphomas. Here, we discuss the numerous targets and pathways which may offer the prospect of directly inhibiting the mechanisms identified promoting and sustaining marginal zone lymphomagenesis. In particular, we focus on the agents that may have at least a theoretical application in the disease. Various dysregulated pathways converge to produce an overarching stimulation of nuclear factor κB (NF-κB) and the <i>MYD88-IRAK4 axis</i>, which can be thus leveraged or targeting B-cell receptor signaling through BTK inhibitors (such as ibrutinib, zanubrutinib, acalabrutinib) and PI3K inhibitors (such as idelalisib, copanlisib, duvelisib umbralisib) or via more novel agents in development such as MALT1 inhibitors, SMAC mimetics, NIK inhibitors, IRAK4 or MYD88 inhibitors. NOTCH signaling is also crucial for marginal zone cells, but no clinical data are available with NOTCH inhibitors such as the γ-secretase inhibitor PF-03084014 or the NICD inhibitor CB-103. The hypermethylation phenotype, the overexpression of the PRC2-complex or the presence of <i>TET2</i> mutations reported in MZL subsets make epigenetic agents (demethylating agents, EZH2 inhibitors, HDAC inhibitors) also potential therapeutic tools for MZL patients.</p>","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"4 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2020-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/06/EMS136368.PMC7611845.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39532685","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}
Marginal zone lymphoma is a term applied to different B-cell low-grade lymphoma disorders with some common features, originated around reactive follicles, composed by small/medium size cells with specific immunophenotype, Ig genes stereotypes and somatic mutation of genes (NOTCH2, KLF2, TNFAIP3...) involved in marginal zone differentiation and NF-kB activation. Marginal zone lymphoma differential diagnosis is based on an integration of clinical, morphological and molecular features. Here we describe the current status of splenic and nodal marginal zone lymphoma (NMZL) diagnosis, reviewing also the markers (MNDA, T-Bet, IRTA1) that facilitate their recognition and diagnosis. Splenic marginal zone lymphoma (SMZL) is a disseminated lymphoma since the initial diagnosis, with both bone marrow and peripheral blood infiltration at diagnosis in almost every case. In contrast, NMZL is frequently a tumor restricted to lymph nodes, where bone marrow and/or peripheral blood involvement is only seen ad advanced stages. Both SMZL and NMZL have a spectrum of clinical presentations ranging from subclinical monoclonal B-cell lymphocytosis at earlier stages to aggressive disorders in advanced stages where p53 mutations, increased CD30 expression or EBV presence are frequently detected.
{"title":"The complex pathology and differential diagnosis of splenic and nodal marginal zone lymphoma","authors":"M. Mollejo, M. Piris","doi":"10.21037/AOL-20-17","DOIUrl":"https://doi.org/10.21037/AOL-20-17","url":null,"abstract":"Marginal zone lymphoma is a term applied to different B-cell low-grade lymphoma disorders with some common features, originated around reactive follicles, composed by small/medium size cells with specific immunophenotype, Ig genes stereotypes and somatic mutation of genes (NOTCH2, KLF2, TNFAIP3...) involved in marginal zone differentiation and NF-kB activation. Marginal zone lymphoma differential diagnosis is based on an integration of clinical, morphological and molecular features. Here we describe the current status of splenic and nodal marginal zone lymphoma (NMZL) diagnosis, reviewing also the markers (MNDA, T-Bet, IRTA1) that facilitate their recognition and diagnosis. Splenic marginal zone lymphoma (SMZL) is a disseminated lymphoma since the initial diagnosis, with both bone marrow and peripheral blood infiltration at diagnosis in almost every case. In contrast, NMZL is frequently a tumor restricted to lymph nodes, where bone marrow and/or peripheral blood involvement is only seen ad advanced stages. Both SMZL and NMZL have a spectrum of clinical presentations ranging from subclinical monoclonal B-cell lymphocytosis at earlier stages to aggressive disorders in advanced stages where p53 mutations, increased CD30 expression or EBV presence are frequently detected.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86764213","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}
Christina Lee, Xiangao Huang, Maurizio Di Liberto, Peter Martin, Selina Chen-Kiang
Targeting the cell cycle represents a rational approach to mantle cell lymphoma (MCL) therapy, as aberrant expression of cyclin D1 and dysregulation of CDK4 underlie cell cycle progression and proliferation of MCL cells. Although cell cycle cancer therapy was historically ineffective due to a lack of selective and effective drugs, this landscape changed with the advent of selective and potent small-molecule oral CDK4/6 inhibitors. Here, we review the anti-tumor activities and clinical data of selective CDK4/6 inhibitors in MCL. We summarize the known mechanism of action of palbociclib, the most specific CDK4/6 inhibitor to date, and the strategy to leverage this specificity to reprogram MCL for a deeper and more durable clinical response to partner drugs. We also discuss integrative longitudinal functional genomics as a strategy to discover tumor-intrinsic genomic biomarkers and tumor-immune interactions that potentially contribute to the clinical response to palbociclib in combination therapy for MCL. Understanding the genomic basis for targeting CDK4/6 and the mechanisms of action and resistance in MCL may advance personalized therapy for MCL and shed light on drug resistance in other cancers.
{"title":"Targeting CDK4/6 in mantle cell lymphoma.","authors":"Christina Lee, Xiangao Huang, Maurizio Di Liberto, Peter Martin, Selina Chen-Kiang","doi":"10.21037/aol.2019.12.01","DOIUrl":"https://doi.org/10.21037/aol.2019.12.01","url":null,"abstract":"<p><p>Targeting the cell cycle represents a rational approach to mantle cell lymphoma (MCL) therapy, as aberrant expression of cyclin D1 and dysregulation of CDK4 underlie cell cycle progression and proliferation of MCL cells. Although cell cycle cancer therapy was historically ineffective due to a lack of selective and effective drugs, this landscape changed with the advent of selective and potent small-molecule oral CDK4/6 inhibitors. Here, we review the anti-tumor activities and clinical data of selective CDK4/6 inhibitors in MCL. We summarize the known mechanism of action of palbociclib, the most specific CDK4/6 inhibitor to date, and the strategy to leverage this specificity to reprogram MCL for a deeper and more durable clinical response to partner drugs. We also discuss integrative longitudinal functional genomics as a strategy to discover tumor-intrinsic genomic biomarkers and tumor-immune interactions that potentially contribute to the clinical response to palbociclib in combination therapy for MCL. Understanding the genomic basis for targeting CDK4/6 and the mechanisms of action and resistance in MCL may advance personalized therapy for MCL and shed light on drug resistance in other cancers.</p>","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/aol.2019.12.01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38252921","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":"Application of the CARE guideline as reporting standard in the Annals of Lymphoma","authors":"","doi":"10.21037/aol.2019.11.01","DOIUrl":"https://doi.org/10.21037/aol.2019.11.01","url":null,"abstract":"","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89291761","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}
Approximately 65% of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line therapy and achieve an overall survival comparable to the general population. Of the 35% of patients who fail front-line therapy, less than a quarter can be salvaged and cured by intensive chemotherapy followed by an autologous stem cell transplant. Patients who are transplant-ineligible (including elderly patients with co-morbidities, patients who are chemotherapy-refractory or those who have failed transplant) represent an unmet medical need population with a very poor outcome. While chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in this setting, many patients will be unsuitable or relapse after CAR-T therapy. These patients are ideal candidates for less toxic novel therapies and a more tailored personalized approach, recognizing the biological heterogeneity of DLBCL. In this review, we will briefly summarize the standard management options for relapsed/refractory DLBCL and then focus on the novel therapies currently in development. We aim to discuss the biological rationale and available clinical data for the most promising agents, including monoclonal antibodies, antibody-drug conjugates (ADC), pathway inhibitors, immunomodulatory agents and epigenetic modifiers.
{"title":"New drugs for the management of relapsed or refractory diffuse large B-cell lymphoma","authors":"C. Sarkozy, L. Sehn","doi":"10.21037/aol.2019.09.01","DOIUrl":"https://doi.org/10.21037/aol.2019.09.01","url":null,"abstract":"Approximately 65% of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line therapy and achieve an overall survival comparable to the general population. Of the 35% of patients who fail front-line therapy, less than a quarter can be salvaged and cured by intensive chemotherapy followed by an autologous stem cell transplant. Patients who are transplant-ineligible (including elderly patients with co-morbidities, patients who are chemotherapy-refractory or those who have failed transplant) represent an unmet medical need population with a very poor outcome. While chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in this setting, many patients will be unsuitable or relapse after CAR-T therapy. These patients are ideal candidates for less toxic novel therapies and a more tailored personalized approach, recognizing the biological heterogeneity of DLBCL. In this review, we will briefly summarize the standard management options for relapsed/refractory DLBCL and then focus on the novel therapies currently in development. We aim to discuss the biological rationale and available clinical data for the most promising agents, including monoclonal antibodies, antibody-drug conjugates (ADC), pathway inhibitors, immunomodulatory agents and epigenetic modifiers.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82239147","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}
Peripheral T-cell lymphomas (PTCL) remain a diagnostic challenge, and the most common subtype remains “unspecified”. However, improved understanding of the transcriptional and genetic landscape among the PTCL’s supports an ontological classification scheme that is based on the “cell of origin” and facilitates the identification of subset-specific therapeutic vulnerabilities. Therefore, it is anticipated that identification of the “cell of origin” will become increasingly important as a predictive biomarker as targeted agents become increasingly available, thus highlighting the need for expert hematopathology review and appropriate disease classification. Herein, we present a PTCL case as a framework within which to review recent developments in PTCL classification and survey the current therapeutic landscape.
{"title":"A survey of the therapeutic landscape in peripheral T-cell lymphomas: the importance of expert hematopathology review in the era of targeted therapies and precision medicine","authors":"A. Scott, C. Ross, Ali M. Gabali, R. Wilcox","doi":"10.21037/aol.2019.10.01","DOIUrl":"https://doi.org/10.21037/aol.2019.10.01","url":null,"abstract":"Peripheral T-cell lymphomas (PTCL) remain a diagnostic challenge, and the most common subtype remains “unspecified”. However, improved understanding of the transcriptional and genetic landscape among the PTCL’s supports an ontological classification scheme that is based on the “cell of origin” and facilitates the identification of subset-specific therapeutic vulnerabilities. Therefore, it is anticipated that identification of the “cell of origin” will become increasingly important as a predictive biomarker as targeted agents become increasingly available, thus highlighting the need for expert hematopathology review and appropriate disease classification. Herein, we present a PTCL case as a framework within which to review recent developments in PTCL classification and survey the current therapeutic landscape.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90469436","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}
V. Orellana-Noia, J. Kluin-Nelemans, Michael E. Williams
A number of recent therapeutic advances have improved outcomes for mantle cell lymphoma (MCL), both in the front-line and relapsed/refractory settings. With a median age of 65 at diagnosis, many patients are considered ineligible for autologous stem cell transplantation and at risk for increased toxicity from the intensified front-line therapies which are effective in younger patients. In recent years, the field has gained an understanding of the clinical and biologic heterogeneity that in turn may inform front-line therapy and provide options that balance treatment intensity with the special risks faced by older or medically unfit MCL patients. Noting that several key studies are currently underway which could alter this clinical landscape, this review will discuss the current state and evolving standards of care for elderly patients with previously-untreated MCL.
{"title":"Front-line therapy in elderly patients with mantle cell lymphoma","authors":"V. Orellana-Noia, J. Kluin-Nelemans, Michael E. Williams","doi":"10.21037/AOL.2019.06.02","DOIUrl":"https://doi.org/10.21037/AOL.2019.06.02","url":null,"abstract":"A number of recent therapeutic advances have improved outcomes for mantle cell lymphoma (MCL), both in the front-line and relapsed/refractory settings. With a median age of 65 at diagnosis, many patients are considered ineligible for autologous stem cell transplantation and at risk for increased toxicity from the intensified front-line therapies which are effective in younger patients. In recent years, the field has gained an understanding of the clinical and biologic heterogeneity that in turn may inform front-line therapy and provide options that balance treatment intensity with the special risks faced by older or medically unfit MCL patients. Noting that several key studies are currently underway which could alter this clinical landscape, this review will discuss the current state and evolving standards of care for elderly patients with previously-untreated MCL.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88803441","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}
Central nervous system involvement is a hallmark of worse prognosis in all types of cancer, including diffuse large B-cell lymphoma. Secondary central nervous system lymphoma diagnosed both at first presentation and at relapse in diffuse large B-cell lymphoma patients represents an important unmeet clinical need. It is a rare, early, fatal, and preventable condition. Central nervous system dissemination occurs in 5% of all diffuse large B-cell lymphoma, usually during primary therapy or the first year of follow-up, and most of affected patients die of lymphoma in everyday practice, with a 4-year overall survival close to 40% in prospective trials. A diffuse use of an efficient prophylaxis to prevent this complication could reduce overall mortality in diffuse large B-cell lymphoma. However, prophylaxis strategies are associated with some forms of toxicity, which is severe in some subjects. Accordingly, this option should be used only in some subgroups of patients with “high risk” of developing central nervous system involvement. Unfortunately, variables and scores proposed to identify “high risk” patients show a low diagnostic sensitivity, resulting in an overtreatment for a high proportion of patients. Moreover, there is still no consensus on the most effective prophylaxis modality to prevent central nervous system dissemination as well as on the standard of care that can be used in patients with secondary central nervous system lymphoma. A few prospective trials focused on new approaches to secondary central nervous system lymphoma patients have been published. Overall, these studies suggest that combinations of drugs with good central nervous system penetrance and anti-lymphoma efficacy are associated with improved outcome, in particular in patients managed with autologous stem cell transplantation. In this review, we discuss the current open questions in the field, propose risk stratification and management algorithms and analyze evidence supporting therapeutic choices in secondary central nervous system lymphoma patients.
{"title":"Risk stratification and management algorithms for patients with diffuse large B-cell lymphoma and CNS involvement","authors":"T. Calimeri, P. Lopedote, A. Ferreri","doi":"10.21037/AOL.2019.06.01","DOIUrl":"https://doi.org/10.21037/AOL.2019.06.01","url":null,"abstract":"Central nervous system involvement is a hallmark of worse prognosis in all types of cancer, including diffuse large B-cell lymphoma. Secondary central nervous system lymphoma diagnosed both at first presentation and at relapse in diffuse large B-cell lymphoma patients represents an important unmeet clinical need. It is a rare, early, fatal, and preventable condition. Central nervous system dissemination occurs in 5% of all diffuse large B-cell lymphoma, usually during primary therapy or the first year of follow-up, and most of affected patients die of lymphoma in everyday practice, with a 4-year overall survival close to 40% in prospective trials. A diffuse use of an efficient prophylaxis to prevent this complication could reduce overall mortality in diffuse large B-cell lymphoma. However, prophylaxis strategies are associated with some forms of toxicity, which is severe in some subjects. Accordingly, this option should be used only in some subgroups of patients with “high risk” of developing central nervous system involvement. Unfortunately, variables and scores proposed to identify “high risk” patients show a low diagnostic sensitivity, resulting in an overtreatment for a high proportion of patients. Moreover, there is still no consensus on the most effective prophylaxis modality to prevent central nervous system dissemination as well as on the standard of care that can be used in patients with secondary central nervous system lymphoma. A few prospective trials focused on new approaches to secondary central nervous system lymphoma patients have been published. Overall, these studies suggest that combinations of drugs with good central nervous system penetrance and anti-lymphoma efficacy are associated with improved outcome, in particular in patients managed with autologous stem cell transplantation. In this review, we discuss the current open questions in the field, propose risk stratification and management algorithms and analyze evidence supporting therapeutic choices in secondary central nervous system lymphoma patients.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75948067","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}
Over the past 10–15 years, there has been a surge in the development and utilization of immunologic strategies aimed at harnessing the power of the cellular immune system to treat a remarkable range of human disease. As is being seen throughout the spectrum of malignant hematology, there are several emerging immunologic therapies which may ultimately revolutionize the treatment and clinical outcomes of patients with mantle cell lymphoma (MCL). Three unique immunologic approaches—checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific T-cell engager (BiTE) molecules—are currently on the forefront of clinical investigation. While preclinical studies have suggested a mechanistic role for immunomodulation via checkpoint blockade (PD-L1, PD-1) in patients with MCL, clinical data thus far suggests only modest success. CAR T-cell therapies, engineered to directly overcome deficiencies in the anti-tumor T-cell response, appear to show early promise and large trials actively enrolling MCL patients are currently in progress. BiTE molecules, which seek to engage and directly activate the cytotoxic power of T-cells upon bispecific interaction with tumor antigen, are being explored in treatment of MCL and early efficacy data seems encouraging as well.
{"title":"Immunologic treatment strategies in mantle cell lymphoma: checkpoint inhibitors, chimeric antigen receptor (CAR) T-cells, and bispecific T-cell engager (BiTE) molecules","authors":"J. Pritchett, S. Ansell","doi":"10.21037/AOL.2019.05.01","DOIUrl":"https://doi.org/10.21037/AOL.2019.05.01","url":null,"abstract":"Over the past 10–15 years, there has been a surge in the development and utilization of immunologic strategies aimed at harnessing the power of the cellular immune system to treat a remarkable range of human disease. As is being seen throughout the spectrum of malignant hematology, there are several emerging immunologic therapies which may ultimately revolutionize the treatment and clinical outcomes of patients with mantle cell lymphoma (MCL). Three unique immunologic approaches—checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific T-cell engager (BiTE) molecules—are currently on the forefront of clinical investigation. While preclinical studies have suggested a mechanistic role for immunomodulation via checkpoint blockade (PD-L1, PD-1) in patients with MCL, clinical data thus far suggests only modest success. CAR T-cell therapies, engineered to directly overcome deficiencies in the anti-tumor T-cell response, appear to show early promise and large trials actively enrolling MCL patients are currently in progress. BiTE molecules, which seek to engage and directly activate the cytotoxic power of T-cells upon bispecific interaction with tumor antigen, are being explored in treatment of MCL and early efficacy data seems encouraging as well.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89003395","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}
Bendamustine-rituximab is being increasingly used in the treatment of indolent non-Hodgkin’s lymphoma, both first line and in cases of relapsed or refractory disease. We report a case of bendamustine associated sensorineural hearing loss in a 41-year-old lady with follicular lymphoma. A correlation between bendamustine and ototoxicity, in a patient with previously normal hearing, has not been demonstrated within the literature. However, there is significant evidence of ototoxicity and neurotoxicity caused by other alkylating agent and purine analogue drugs and there is growing evidence for the role of bendamustine in the development of neurotoxicity. As such, the development of neurologic sequelae in any patient receiving bendamustine therapy should prompt urgent review of the ongoing chemotherapy regime.
{"title":"Sensorineural hearing loss in a patient with follicular lymphoma treated with bendamustine and rituximab","authors":"Gabrielle Rule, Aaron Esmaili, C. Cheah","doi":"10.21037/AOL.2019.04.01","DOIUrl":"https://doi.org/10.21037/AOL.2019.04.01","url":null,"abstract":"Bendamustine-rituximab is being increasingly used in the treatment of indolent non-Hodgkin’s lymphoma, both first line and in cases of relapsed or refractory disease. We report a case of bendamustine associated sensorineural hearing loss in a 41-year-old lady with follicular lymphoma. A correlation between bendamustine and ototoxicity, in a patient with previously normal hearing, has not been demonstrated within the literature. However, there is significant evidence of ototoxicity and neurotoxicity caused by other alkylating agent and purine analogue drugs and there is growing evidence for the role of bendamustine in the development of neurotoxicity. As such, the development of neurologic sequelae in any patient receiving bendamustine therapy should prompt urgent review of the ongoing chemotherapy regime.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"75 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87834743","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}
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