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Journal of Medicine and Life 2018Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL... (Review)
Review
Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.
Topics: Endoscopy; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Prognosis
PubMed: 30364585
DOI: 10.25122/jml-2018-0035 -
Cancer Dec 2018Emerging biologic subsets and new prognostic markers are significantly and adversely affecting curability after standard chemoimmunotherapy for aggressive B-cell... (Review)
Review
Emerging biologic subsets and new prognostic markers are significantly and adversely affecting curability after standard chemoimmunotherapy for aggressive B-cell lymphomas. The identification of concurrent MYC and B-cell CLL/lymphoma 2 (BCL2) deregulation, whether at a genomic or protein level, has opened a new era of investigation within the most common subtype of aggressive B-cell lymphomas. Double-hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B-cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B-cell lymphomas (DLBCLs), and long-term survivors are rare. Double-expressor lymphoma (DEL), defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, is not a distinct entity in the current World Health Organization classification but accounts for 20% to 30% of DLBCL cases and also has poor outcomes. There are many practical considerations related to identifying, determining the prognosis of, and managing DHL and DEL.
Topics: Clinical Trials as Topic; Gene Expression Regulation, Neoplastic; Humans; Lymphoma, B-Cell; Prognosis; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; Up-Regulation
PubMed: 30252929
DOI: 10.1002/cncr.31646 -
Advances in Clinical and Experimental... Aug 2019Although gastrointestinal (GI) tract is the most common extranodal site involved in non-Hodgkin lymphoma (NHL), primary gastrointestinal NHL (gNHL) is a rare problem... (Review)
Review
Although gastrointestinal (GI) tract is the most common extranodal site involved in non-Hodgkin lymphoma (NHL), primary gastrointestinal NHL (gNHL) is a rare problem which concerns about 10-15% of NHL patients and 30-40% of extranodal NHL patients. Lymphoid neoplasms may consist of mature B, T and (less commonly) extranodal NK/T cells. The most common diagnoses are diffuse large B-cell lymphoma and marginal zone lymphoma (MALT), but many other lymphomas may be found in the GI tract. There are a few well-known risk factors of gNHL and some of them affect treatment. The most frequent sites of occurrence are the stomach followed by small intestine and ileocecal region. In the last 2 decades, there has been a rapid development in the diagnosis, staging and management of GI lymphoma, but still some of such lymphomas, especially T-cell ones, are a therapeutic challenge. In this review, we present clinical and pathological features of GI lymphomas. We also describe the current status in diagnosis and treatment.
Topics: Gastrointestinal Neoplasms; Humans; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse
PubMed: 31414733
DOI: 10.17219/acem/94068 -
Advances in Therapy Oct 2017Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various... (Review)
Review
UNLABELLED
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue.
FUNDING
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Topics: Animals; Antineoplastic Agents, Immunological; B-Lymphocytes; Hematologic Neoplasms; History, 20th Century; History, 21st Century; Humans; Lymphoma, B-Cell; Rituximab
PubMed: 28983798
DOI: 10.1007/s12325-017-0612-x -
Journal of Hematology & Oncology Aug 2021B-cell lymphoma is a group of hematological malignancies with high clinical and biological heterogeneity. The pathogenesis of B-cell lymphoma involves a complex... (Review)
Review
B-cell lymphoma is a group of hematological malignancies with high clinical and biological heterogeneity. The pathogenesis of B-cell lymphoma involves a complex interaction between tumor cells and the tumor microenvironment (TME), which is composed of stromal cells and extracellular matrix. Although the roles of the TME have not been fully elucidated, accumulating evidence implies that TME is closely relevant to the origination, invasion and metastasis of B-cell lymphoma. Explorations of the TME provide distinctive insights for cancer therapy. Here, we epitomize the recent advances of TME in B-cell lymphoma and discuss its function in tumor progression and immune escape. In addition, the potential clinical value of targeting TME in B-cell lymphoma is highlighted, which is expected to pave the way for novel therapeutic strategies.
Topics: Animals; Antineoplastic Agents; B-Lymphocytes; Drug Discovery; Humans; Immunotherapy; Lymphoma, B-Cell; Molecular Targeted Therapy; Tumor Escape; Tumor Microenvironment
PubMed: 34404434
DOI: 10.1186/s13045-021-01134-x -
British Journal of Haematology Jun 2020Aggressive B-cell non-Hodgkin lymphoma (B-NHL) accounts for ≈60% of NHL in children/adolescents. In newly diagnosed Burkitt lymphoma and diffuse large B-cell lymphoma,... (Review)
Review
Aggressive B-cell non-Hodgkin lymphoma (B-NHL) accounts for ≈60% of NHL in children/adolescents. In newly diagnosed Burkitt lymphoma and diffuse large B-cell lymphoma, short intensive multiagent chemotherapy is associated with a five-year event-free survival of around 90%. Very few children/adolescents with aggressive B-NHL show a relapsed/refractory (r/r) disease. The outcome is poor, with cure rates <30%, and there is no standard of care. Rituximab-containing salvage regimens may provide a complete/partial response in 60-70% of cases. However, long-term survival is <10% for non-transplanted patients. Autologous or allogeneic haematopoietic stem cell transplant is, nowadays, the best option for responding patients, with survival rates around 50%. The benefit of autologous versus allogeneic HSCT is not clear. Numerous novel therapies for r/r B-NHL are currently being tested in adults, including next-generation monoclonal antibodies, novel cellular therapy strategies and therapies directed against new targets. Some are under investigation also in children/adolescents, with promising preliminary results.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Combined Modality Therapy; Cranial Irradiation; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Prognosis; Recurrence; Risk Factors; Salvage Therapy; Therapies, Investigational; Treatment Outcome; Young Adult
PubMed: 32141616
DOI: 10.1111/bjh.16461 -
Annals of Oncology : Official Journal... Sep 2015
Topics: Humans; Lymphoma, Large B-Cell, Diffuse
PubMed: 26314773
DOI: 10.1093/annonc/mdv304 -
Journal of Clinical Oncology : Official... Dec 2019Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need....
PURPOSE
Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade.
METHODS
In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity.
RESULTS
The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival.
CONCLUSION
Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Disease Progression; Drug Resistance, Neoplasm; Europe; Female; Humans; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Risk Assessment; Risk Factors; South America; Time Factors; United States; Young Adult
PubMed: 31609651
DOI: 10.1200/JCO.19.01389 -
Blood Oct 2020Chimeric antigen receptor (CAR) T cells targeting CD19 have achieved breakthroughs in the treatment of hematological malignancies, such as relapsed/refractory...
Chimeric antigen receptor (CAR) T cells targeting CD19 have achieved breakthroughs in the treatment of hematological malignancies, such as relapsed/refractory non-Hodgkin lymphoma (r/rNHL); however, high rates of treatment failure and recurrence after CAR T-cell therapy are considerable obstacles to overcome. In this study, we designed a series of tandem CARs (TanCARs) and found that TanCAR7 T cells showed dual antigen targeting of CD19 and CD20, as well as formed superior and stable immunological synapse (IS) structures, which may be related to their robust antitumor activity. In an open-label single-arm phase 1/2a trial (NCT03097770), we enrolled 33 patients with r/rNHL; 28 patients received an infusion after conditioning chemotherapy. The primary objective was to evaluate the safety and tolerability of TanCAR7 T cells. Efficacy, progression-free survival, and overall survival were evaluated as secondary objectives. Cytokine release syndrome occurred in 14 patients (50%): 36% had grade 1 or 2 and 14% had grade 3. No cases of CAR T-cell-related encephalopathy syndrome (CRES) of grade 3 or higher were confirmed in any patient. One patient died from a treatment-associated severe pulmonary infection. The overall response rate was 79% (95% confidence interval [CI], 60-92%), and the complete response rate was 71%. The progression-free survival rate at 12 months was 64% (95% CI, 43-79%). In this study, TanCAR7 T cells elicited a potent and durable antitumor response, but not grade 3 or higher CRES, in patients with r/rNHL.
Topics: Adult; Aged; Animals; Antigens, CD19; Antigens, CD20; Cell Culture Techniques; Cell Degranulation; Cytotoxicity, Immunologic; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Humans; Immunophenotyping; Immunotherapy, Adoptive; Lymphoma, B-Cell; Male; Mice; Middle Aged; Prognosis; Receptors, Chimeric Antigen; Recurrence; Retreatment; T-Lymphocytes; Treatment Outcome; Xenograft Model Antitumor Assays
PubMed: 32556247
DOI: 10.1182/blood.2020005278 -
Blood Reviews Mar 2017Diffuse large B-cell lymphomas with aberrations in MYC, BCL2 and/or BCL6 by genetic alterations or protein expression represent a group of high grade B-cell lymphomas... (Review)
Review
Diffuse large B-cell lymphomas with aberrations in MYC, BCL2 and/or BCL6 by genetic alterations or protein expression represent a group of high grade B-cell lymphomas with inferior outcomes when treated with standard RCHOP chemotherapy. As a result, intensified induction regimens have been suggested in an effort to improve outcomes. Conclusions to date have largely been drawn from retrospective data although prospective data is slowly starting to emerge. Chemoimmunotherapy refractoriness is problematic and relapse rates are high. Patients with double hit lymphoma appear to have increased risk of CNS involvement and prophylaxis is recommended. There is insufficient evidence available to date to strongly recommend for or against consolidative stem cell transplant in this population. Collaborative clinical trials will be needed to establish a preferred therapeutic regimen and an appropriate standard of care in this unique group of patients with DLBCL.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Genes, myc; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Neoplasm Grading; Oncogene Proteins, Fusion; Prognosis; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6; Translocation, Genetic; Treatment Outcome
PubMed: 27717585
DOI: 10.1016/j.blre.2016.09.004