Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types. The management of double hit lymphomas, which almost exclusively fall under the GCB category, is discussed, together with the double expresser phenotype, which is usually grouped under the non-GCB type. The role of lenalidomide and ibrutinib in the management of the non-GCB type is examined. We also discuss the front-line management of primary mediastinal large cell lymphoma using the EPOCH (etoposide, prednisolone, Oncovin [vincristine], cyclophosphamide, hydroxydaunorubicin [doxorubicin]) regimen and examine new salvage data on immune checkpoint inhibitors for this clinical subtype. The prognosis, clinical features, and management of de novo CD5+ DLBCL are discussed, and newer and promising developments in the management of primary central nervous system lymphomas are presented in detail. The most popular salvage regimens and the application of high-dose chemotherapy with stem cell transplantation are assessed in detail. Finally, data on new treatment tactics such as CART (chimeric antigen receptor T-cell) cells and promising new drugs, including blinatumomab and venetoclax, are presented.
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PMID:Advances in Diagnosis and Management of Diffuse Large B-cell Lymphoma. 2912 66

Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis. Chimeric Antigen Receptor (CAR)-modified T cells (CART cells) that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas. We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART (CART-20) cells to patients with refractory or relapsed CD20+ B-cell lymphoma. Eleven patients were enrolled, and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions. The overall objective response rate was 9 of 11 (81.8%), with 6 complete remissions (CRs) and 3 partial remissions; no severe toxicity was observed. The median progression-free survival lasted for >6 months, and 1 patient had a 27-month continuous CR. A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed. Clinically, the lesions in special sites, specifically the spleen and testicle, were refractory to CART-20 treatment. Collectively, these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study. This study was registered at www.clinicaltrials.org as NCT01735604.
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PMID:Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. 2926 94

Chimeric antigen receptor T-cell strategy targeting CD19 (CART19) has prominent anti-tumor effect for relapsed/refractory B-cell lymphomas. CART19-associated complications have been gradually recognized, however, late-onset complications have not been extensively studied. Herein, for the first time we report a diffuse large B-cell lymphoma patient with terminal ileum involvement obtained rapid remission and developed spontaneous terminal ileal perforation 38 days following CART19 infusion. The late-onset perforation reminds us that, for the safety of CART treatment, more cautions are warranted for the management of delayed GI complications.
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PMID:Delayed Terminal Ileal Perforation in a Relapsed/Refractory B-Cell Lymphoma Patient with Rapid Remission Following Chimeric Antigen Receptor T-Cell Therapy. 2939 60

CAR (chimeric antigen receptor) T cells (CARTs) are genetically engineered T cells that express CARs, with impressive clinical activity in relapsed and refractory hematologic malignancies, primarily acute lymphoblastic leukemia and diffuse large B-cell lymphoma. The most frequent life-threatening adverse events after CART infusion are cytokine release syndrome and CAR-related encephalopathy syndrome, which can occur within hours or days after administration. IL-6 released by macrophages and monocytes plays a major role in the pathogenesis of cytokine release syndrome and CAR-related encephalopathy syndrome, and IL-6 blockade and steroids contribute to fast resolution of symptoms. Critical care management plays an important role in patients receiving CARTs, as up to half of patients might need an admission to the ICU and lifesaving interventions. As new treatment indications and CART constructs enter the clinic, the number of patients requiring ICU admission will rapidly increase, with profound consequences for the use of ICU resources, training requirements, clinical expertise, multidisciplinary collaboration, and hospital organization. Research is also needed to validate at large scale biomarkers that allow doctors to risk-stratify patients for both their risk to develop severe toxicity and their likelihood to respond to therapy.
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PMID:Critical Care Management of Chimeric Antigen Receptor T Cell-related Toxicity. Be Aware and Prepared. 3067 76

Introduction: Blinatumomab, a first-in-class bispecific T cell engager, is a member of a novel class of bispecific antibody constructs with dual binding specificities. While its primary clinical use has been in B cell acute lymphoblastic leukemia, its role in the treatment of B cell non-Hodgkin's Lymphoma (NHL) is less well established.Areas covered: Herein, the authors provide a brief overview of the market, unmet needs, and how blinatumomab fits in to the evolving armamentarium of lymphoma-directed therapies. The authors address its therapeutic role in salvage therapy for relapsed/refractory NHL, as consolidation for high-risk diffuse large B cell lymphoma (DLBCL) following ASCT, and through various combinations with other available agents. Moreover, authors highlight key competitors.Expert opinion: Although blinatumomab showed impressive results in phase I and II studies for relapsed/refractory DLBCL, its future utility remains to be seen in this clinical setting due to lack of phase III trial and FDA approval of CD19 CART therapy. A new CD19/CD3 and several CD20/CD3 bispecific antibodies with longer half-life and resultant easier mode of administration which can overcome the major barriers of its use in clinical practice are in the pipeline and their role in NHL treatment are actively explored.
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PMID:Blinatumomab: a novel therapy for the treatment of non-Hodgkin's lymphoma. 3158 19

Background: The therapeutic efficacy of chimeric antigen receptor (CAR) T-cells targeting CD19 has been illustrated in the treatment of diffuse large B-cell lymphoma (DLBCL). However, there is a 21-35% relapse rate after anti-CD19 CAR T-cell induced remission. In addition, CAR T-cell therapy has severe adverse reactions, such as cytokine release syndrome (CRS) and CART-related encephalopathy syndrome (CRES). Because of the potential mortality associated with severe CRES, patients with primary central nervous system lymphoma (PCNSL) are usually excluded from clinical trials involving CAR T-cell therapy. Here, we report a case of refractory and relapsed primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Case Presentation: The patient is a 67-year-old male who was diagnosed with PCNSL in 2011. He achieved complete remission (CR) after receiving 6 cycles of temozolomide and high-dose methotrexate. In December 2016, he experienced his first relapse and was treated with surgery and multicourse chemotherapy. He achieved CR again after the treatment. However, he experienced a second relapse in August 2017. MRI revealed a residual mass of 26 mm*35 mm*30 mm on the right side of the post-operative cavity and stale hemorrhage in the left basal ganglia. After confirming the expression of CD19 and CD70 in his tumor samples, the patient was given lymphodepletion chemotherapy followed by infusion of 4th generation CD19-CAR T-cells (4SCART19) and 4th generation CD70-CAR T-cells (4SCART70). One month later, the patient had symptomatic improvement, and brain MRI showed CR. Both CART19 and CART70 cells were detected in the 10th month after CAR T-cell infusion. Notably, neither CRS nor CRES occurred during treatment and follow-up. To date, the patient has maintained disease-free survival with more than 17 months of follow-up. Conclusions: The results of this study indicate that combination of CD19- and CD70-specific CAR T-cells may effectively target PCNSL and maintain disease-free survival without inducing CRS or CRES. Therefore, central nervous system lymphoma is not an absolute contraindication for dual-target CAR T-cell therapy.
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PMID:CD19 and CD70 Dual-Target Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Relapsed and Refractory Primary Central Nervous System Diffuse Large B-Cell Lymphoma. 3186 75

Chimeric antigen receptor (CAR)-T cells (CART) remain one of the most advanced and promising forms of adoptive T-cell immunotherapy. CART represent autologous, genetically engineered T lymphocytes expressing CAR, i.e. fusion proteins that combine components and features of T cells as well as antibodies providing their more effective and direct anti-tumour effect. The technology of CART construction is highly advanced in vitro and every element of their structure influence their mechanism of action in vivo. Patients with haematological malignancies are faced with the possibility of disease relapse after the implementation of conventional chemo-immunotherapy. Since the most preferable result of therapy is a partial or complete remission, cancer treatment regimens are constantly being improved and customized to individual patients. This individualization could be ensured by CART therapy. This paper characterized CART strategy in details in terms of their structure, generations, mechanism of action and published the results of clinical trials in haematological malignancies including acute lymphoblastic leukaemia, diffuse large B-cell lymphoma, chronic lymphocytic leukaemia and multiple myeloma.
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PMID:The Application of CAR-T Cells in Haematological Malignancies. 3315 9