V. Lin, M. Anderson, D. Huang, A. Roberts, J. Seymour, C. Tam
{"title":"Venetoclax for the treatment of mantle cell lymphoma","authors":"V. Lin, M. Anderson, D. Huang, A. Roberts, J. Seymour, C. Tam","doi":"10.21037/AOL.2019.03.02","DOIUrl":"https://doi.org/10.21037/AOL.2019.03.02","url":null,"abstract":"While the last decade has seen an explosion in improved therapies for mantle cell lymphoma (MCL), the outlook for patients with relapsed or refractory MCL (R/R MCL) remains poor, especially for those who are older with comorbidities or harbour dysfunction in the TP53 pathway. MCL is one of the B cell malignancies in which there is a high frequency of BCL2 overexpression, and the selective BCL2 inhibitor venetoclax has shown particular promise in the treatment of patients with R/R MCL. As a single agent, the drug is associated with a close to 80% response rate in early phase studies. However, secondary progression due to the development of resistance remains a limiting factor in the usefulness of this agent. Preclinical data has driven the push to combine venetoclax with other novel agents, particularly the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib. This therapeutic combination has increased the rate of complete remissions to over 60% and provides a promising route to meaningful long-term disease control with non-chemotherapy-based treatment.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88552360","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":"Mantle cell lymphoma pathology update in the 2016 WHO classification","authors":"L. Veloza, Inmaculada Ribera‐Cortada, E. Campo","doi":"10.21037/AOL.2019.03.01","DOIUrl":"https://doi.org/10.21037/AOL.2019.03.01","url":null,"abstract":"Mantle cell lymphoma (MCL) is an aggressive mature B-cell neoplasm genetically characterized by the presence of the t(11;14)(q13;q32) that leads to the constitutive overexpression of cyclin D1. The pathological and biological spectrum of this neoplasm has been expanded in recent years. This improvement in the knowledge of the disease has provided a better understanding of the diverse clinical evolution of the patients. The characterization of cyclin D1-negative MCL has led to the identification of cyclin D2 and D3 translocations as alternative mechanisms in this variant. Two major biological and clinical subtypes of the disease have been recognized, conventional and leukemic non-nodal MCL (nnMCL). MCL derives from CD5+ mature B-cells that have bypassed or experienced the germinal center microenvironment, retain a naive or memory-like epigenetic signature and carry a variable load of somatic mutations in the IGHV region; from truly unmutated to highly mutated, respectively. These two subtypes of tumors also differ in their genomic alterations, and clinical behavior, the conventional MCL (cMCL) being more aggressive than the leukemic nnMCL. This review will focus on the new aspects of the pathology of MCL in the updated 2016 WHO classification and its relevance for the clinical practice.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84115743","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 there a role for immunomodulatory drugs in the treatment of mantle cell lymphoma?","authors":"A. Albertsson-Lindblad, M. Jerkeman","doi":"10.21037/AOL.2019.01.01","DOIUrl":"https://doi.org/10.21037/AOL.2019.01.01","url":null,"abstract":"Although survival has improved in patients with mantle cell lymphoma (MCL) during the last two decades, thanks to intensified approach upfront and with anti-CD20 targeted treatment, the disease is still regarded as incurable and for the elderly/unfit patient population, there is need for more tolerable and effective treatment options. Immunomodulatory drugs (IMiDs) have demonstrated activity in MCL and could be regarded as attractive components of combinatory regimens for MCL, in light of their broad spectrum of activity and the potency to synergize with monoclonal antibody treatment. This review focus on the role of lenalidomide (L) as single agent in R/R MCL and in combinatory regimens. To date, one can conclude that L is an active agent in MCL, preferably when combined with anti-CD20 antibody, and may have a role as upfront treatment of elderly/unfit patients. Moreover, regimens including lenalidomide in combination with immunochemotherapy and in chemo-free regimens have shown activity, albeit associated with an increased risk of dose-limiting toxicity in untreated patient populations. Randomized trials evaluating the addition of L upfront, and phase I/II trials on L combined with other novel agents such as BTK- and bcl-2 inhibitors are underway and will further bring insight into the role of IMiDs in MCL.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89105299","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}
Bo-Jung Chen, F. Fend, E. Campo, L. Quintanilla‐Martinez
{"title":"Aggressive B-cell lymphomas—from morphology to molecular pathogenesis","authors":"Bo-Jung Chen, F. Fend, E. Campo, L. Quintanilla‐Martinez","doi":"10.21037/AOL.2018.12.02","DOIUrl":"https://doi.org/10.21037/AOL.2018.12.02","url":null,"abstract":"The2016 revised World Health Organization (WHO) classification of lymphoidmalignancies recognizes several distinct entities within the group of diffuselarge B-cell lymphoma (DLBCL) characterized by unique clinical and pathologicalfeatures. Nevertheless, diffuse large B-cell lymphoma, not otherwise specified(DLBCL, NOS) is the most common aggressive B-cell lymphoma. In the last 20 yearsour understanding of the genetic changes and biology of DLBCL has increasedtremendously. According to the 2016 WHO classification, the diagnosis of DLBCL,NOS, should include cell of origin (COO); germinal centre B-cell (GCB) oractivated B-cell (ABC)/non-GCB subtypes, because of their different molecularfeatures, biologic behavior, prognosis and treatment. High-grade B-celllymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (i.e., double-hit or triple-hit lymphoma, DHL or THL) as well asHGBL, NOS, are two new categories in the 2016 revised WHO classification thatsubstituted the provisional category of B-cell lymphoma, unclassifiable (BCLU)with features intermediate between DLBCL and Burkitt lymphoma (BL), which wasintroduced in the 2008 WHO classification. The pathogenesis and molecularchanges of BL are better understood and led to the recognition of a newprovisional entity called Burkitt-like lymphoma with 11q aberration. In thisarticle, we will review the progress made in the last years within the mostcommonly encountered aggressive B-cell lymphomas, highlighting the betterunderstanding of the underlying disease mechanisms that eventually might be translatedinto more rational and effective therapeutic strategies. Controversial issuesabout fluorescent in situ hybridization (FISH) for the detection of MYC , BCL2 and BCL6 translocations will be addressed, as well as newmolecular techniques used to improve diagnosis and prognostication inaggressive B-cell lymphomas.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85128751","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":"Risk stratification of mantle cell lymphoma (MCL)","authors":"Nora Liebers, P. Dreger, M. Dreyling, S. Dietrich","doi":"10.21037/AOL.2018.12.03","DOIUrl":"https://doi.org/10.21037/AOL.2018.12.03","url":null,"abstract":"Despite of a better understanding of the biology of mantle cell lymphoma (MCL), it remains an incurable disease with very variable disease courses. The biological heterogeneity of MCL requires the identification of prognostic markers for risk stratification and tailored treatment of MCL. The combined MCL International Prognostic Index (MIPI-c) represents a well-established clinical risk stratification model. Based on four clinical parameters: age, performance status, lactate dehydrogenase and leucocyte count combined with the percentage of Ki-67 positive MCL cells the model distinguishes four MCL subgroups with very different outcomes. Further prognostic markers, in particular molecular lesions might help to further improve clinical scoring. We discuss the value of clinical and molecular markers to predict outcome of MCL and how these markers could influence treatment decisions.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89043194","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":"Immunotherapy in non-Hodgkin lymphoma","authors":"C. Jacobson, P. Armand","doi":"10.21037/AOL.2018.12.01","DOIUrl":"https://doi.org/10.21037/AOL.2018.12.01","url":null,"abstract":"The concept of co-opting an immune response to treat cancer has existed for centuries. Modern advances in our understanding of how the immune system is regulated, how a tumor evolves to evade an immune response, and how the immune system can be manipulated, both pharmacologically as well as genetically, have moved this concept from an ideal to reality, sparking a revolution in cancer therapeutics and the field of immuno-oncology. This review will focus both on cellular therapeutics, and specifically chimeric antigen receptor (CAR) T-cells, as well as immune checkpoint inhibition, in non-Hodgkin lymphoma (NHL). The former has had remarkable efficacy in a large number of patients, whereas the benefit of the latter has been restricted to specific histologies. As we learn more about the tumor microenvironment for each of the NHL histologies, mechanisms of resistance, and predictors of response, we will undoubtedly identify new combinations, or new ways to manipulate the immune system, to improve outcomes in these diseases.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89693664","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":"Diffuse large B-cell lymphoma—who should we FISH?","authors":"D. Stephens, Sonali M. Smith","doi":"10.21037/aol.2018.11.01","DOIUrl":"https://doi.org/10.21037/aol.2018.11.01","url":null,"abstract":"Thepoor prognosis and adverse outcomes following standard chemoimmunotherapy forpatients with high-grade B-cell lymphomas harboring rearrangements of MYC and BCL2 and/or BCL6 (HGBL-DH/TH) is now well-established, withless than 20% estimated long term survival following standard therapies.Fortunately, the frequency of HGBL-DH/TH in unselected aggressive B-celllymphomas is relatively uncommon and estimated at 10% of all cases. Thesedouble- and/or triple-hit lymphomas are often, but not universally, associatedwith a clinically aggressive presentation, high-grade morphologic features, orincreased protein expression of the corresponding genes. However, a substantialnumber of patients have no clear indicators of underlying DH/TH. The paradox ofan exceedingly poor prognosis coupled with a relatively uncommon frequencyraises the practical challenge of determining which patient warrants FISHtesting and is an area of substantial controversy and emerging data. Theclinical consequence of missing HGBL-DH/TH is dire, as these patients arelikely undertreated by standard chemoimmunotherapy (RCHOP). However, in acost-conscious era, routine and widespread testing for biologic determinants ofoutcome may not be appropriate, and a critical appraisal of predictors iswarranted. This review will discuss the clinical implications of theserearrangements in aggressive B-cell lymphomas and the potential clinical, pathologic,or biologic predictors of underlying HGBL-DH/TH biology.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74572688","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}
Annals of lymphomaPub Date : 2018-03-01Epub Date: 2018-03-20DOI: 10.21037/aol.2018.03.01
Xiaosheng Wu, Thomas E Witzig
{"title":"A new tool in the cancer immunotherapy toolbox?","authors":"Xiaosheng Wu, Thomas E Witzig","doi":"10.21037/aol.2018.03.01","DOIUrl":"https://doi.org/10.21037/aol.2018.03.01","url":null,"abstract":"","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/aol.2018.03.01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39185141","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}
Annals of lymphomaPub Date : 2017-11-01Epub Date: 2017-11-17DOI: 10.21037/aol.2017.11.01
Melody Becnel, Christopher R Flowers, Loretta J Nastoupil
{"title":"Disparities in lymphoma on the basis of race, gender, HIV status, and sexual orientation.","authors":"Melody Becnel, Christopher R Flowers, Loretta J Nastoupil","doi":"10.21037/aol.2017.11.01","DOIUrl":"https://doi.org/10.21037/aol.2017.11.01","url":null,"abstract":"<p><p>Lymphoid malignancies account for the sixth leading cause of death in the US, and, although survival is improving overall, this trend is not applicable to all patients. In this review, we describe disparities in the initial presentation, treatment, and outcomes across a diverse group of lymphoma patients on the basis of gender, race, HIV status, and sexual orientation. Identifying these disparities will hopefully lead to improved outcomes in these groups of lymphoma patients in the future.</p>","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/aol.2017.11.01","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35968737","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}
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