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Mantle cell lymphoma-Advances in molecular biology, prognostication and treatment approaches.

Hematol Oncol 2021 Jun;39 Suppl 1:31-38

Department of Medicine III, LMU Hospital, Munich, Germany.

Mantle cell lymphoma (MCL) is clinically characterized by its heterogenous behavior with courses ranging from indolent cases that do not require therapy for years to highly aggressive MCL with very limited prognosis. A better understanding of the complex biology of MCL has already led to the approval of several innovative agents, expanding the landscape of MCL therapies and improving therapeutic options especially for refractory or relapsed disease. Nevertheless, to further optimize MCL treatment, early identification of individual risk profile and risk-adapted, patient-tailored choice of therapeutic strategy needs to be prospectively incorporated in clinical patient management. Read More

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Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase 1, First-in-Human Study.

Clin Cancer Res 2021 Jun 3. Epub 2021 Jun 3.

Haematology, Peter MacCallum Centre, Melbourne.

Purpose: We previously reported a 44% overall response rate (ORR) with venetoclax in a phase 1 study of relapsed/refractory NHL. Complete remission (CR) was observed in patients with mantle cell lymphoma ([MCL], 21%, n=6/28) and follicular lymphoma ([FL], 17%, n=5/29), and partial response (PR) noted in several patients with Waldenström macroglobulinemia (WM), and marginal zone lymphoma (MZL). Here, we report the long-term outcomes of these four cohorts. Read More

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CAR T-Cells for CNS Lymphoma: Driving into New Terrain?

Cancers (Basel) 2021 May 20;13(10). Epub 2021 May 20.

Department of Neurosurgery, Division of Neuro-Oncology, Ludwig Maximilians University School of Medicine, Marchioninistrasse, 1581377 Munich, Germany.

Primary CNS lymphomas (PCNSL) represent a group of extranodal non-Hodgkin lymphomas and secondary CNS lymphomas refer to secondary involvement of the neuroaxis by systemic disease. CNS lymphomas are associated with limited prognosis even after aggressive multimodal therapy. Chimeric antigen receptor (CAR) T-cells have proven as a promising therapeutic avenue in hematological B-cell malignancies including diffuse large B-cell lymphoma, B-cell acute lymphoblastic leukemia, and mantle-cell lymphoma. Read More

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Identification of miRNA-34a and miRNA-155 as prognostic markers for mantle cell lymphoma.

J Int Med Res 2021 May;49(5):3000605211016390

Department of Hematology, Shanxi Provincial People's Hospital Affiliated with Shanxi Medical University, Taiyuan 030012, China.

Objective: MicroRNAs (miRNAs) with functional relevance have not been previously identified in mantle cell lymphoma (MCL). Here, we aimed to evaluate the relationships between miR-34a and miR-155-5p and MCL clinicopathology and prognosis.

Methods: Seventy-five paraffin-embedded tissue samples from patients with MCL who completed at least four cycles of chemotherapy from January 2006 to October 2016, and 27 samples from control patients with reactive lymphoid hyperplasia (RLH), were collected. Read More

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Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials.

J Infect Public Health 2021 Jun 20;14(6):740-748. Epub 2021 Apr 20.

Department of Pharmacology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, Haryana 133207, India.

Background: Lopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated.

Methods: The databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. Read More

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Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma.

Nat Commun 2021 05 17;12(1):2877. Epub 2021 May 17.

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Read More

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Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BMC Cancer 2021 May 17;21(1):566. Epub 2021 May 17.

Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore City, 169610, Singapore.

Background: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. Read More

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Intravenous busulfan-based conditioning with autologous stem cell transplantation for refractory B-cell lymphoma with central nervous system involvement.

J Med Invest 2021 ;68(1.2):196-201

Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

The prognosis of relapsed or refractory lymphoma with central nervous system (CNS) involvement remains poor because of the lack of anticancer drugs with sufficient CNS penetration. [Case 1] A 65-year-old man was diagnosed with Stage IV mantle cell lymphoma. After two courses of chemotherapy and autologous hematopoietic stem cell (HSC) collection, urinary retention with fever developed. Read More

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January 2021

Treatment of Secondary Immune Thrombocytopenia with Non-Hodgkin Lymphoma: A Case Report and Literature Review.

Intern Med 2021 15;60(10):1583-1588. Epub 2021 May 15.

Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Japan.

Secondary immune thrombocytopenic purpura (ITP) with non-Hodgkin lymphoma (NHL) is a rare disease. Although some treatment regimens are available for primary ITP, the treatment strategy for secondary ITP remains unconfirmed. We herein report a 79-year-old man who was diagnosed with secondary ITP with mantle cell lymphoma. Read More

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Intensive induction regimens after deferring initial therapy for mantle cell lymphoma are not associated with improved survival.

Eur J Haematol 2021 May 11. Epub 2021 May 11.

Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, US.

Introduction: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy.

Methods: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Read More

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The expression of NTAL and its protein interactors is associated with clinical outcomes in acute myeloid leukemia.

Mol Cell Proteomics 2021 May 7:100091. Epub 2021 May 7.

Department of Biochemistry and Immunology, Ribeirão Preto Medical School , University of São Paulo, Ribeirão Preto, Brazil;; Department of Internal Medicine, Ribeirão Preto Medical School and Center for Cell Based Therapy, University of São Paulo, Ribeirão Preto, Brazil;. Electronic address:

Non-T cell activation linker (NTAL) membrane protein depletion from lipid rafts by alkylphospholipids or downregulation by shRNA-knockdown decreases cell viability through regulation of the Akt/PI3K pathway in mantle cell lymphoma and acute promyelocytic leukemia cells. Here, we confirmed that the knockdown of NTAL in acute myeloid leukemia (AML) cell lines was associated with decreased cell proliferation and survival. Similarly, a xenograft model using AML cells transduced with NTAL-shRNA and transplanted into NSG immunodeficient mice led to a 1. Read More

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Real-world evidence on survival, adverse events, and health care burden in Medicare patients with mantle cell lymphoma.

Leuk Lymphoma 2021 Jun 8;62(6):1325-1334. Epub 2021 May 8.

Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX, USA.

Most data on overall survival (OS) and adverse events (AEs) in patients with mantle cell lymphoma (MCL) are from controlled trials; therefore, in this population-based study, we retrospectively assessed treatment patterns, OS, and AEs in MCL patients initiating systemic treatment during 2013-2015 using the United States Medicare claims database. Among 1390 eligible patients (median age = 74 years), chemoimmunotherapy with bendamustine/rituximab (BR) was the preferred choice in first-line (35.3%), followed by ibrutinib (33. Read More

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Cellular Therapies for Mantle Cell Lymphoma.

Transplant Cell Ther 2021 May 6;27(5):363-370. Epub 2021 Feb 6.

Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, Florida. Electronic address:

Mantle cell lymphoma (MCL) is a subtype of B cell non-Hodgkin lymphoma characterized by a heterogeneous clinical presentation. Patients who demonstrate an objective response to induction therapy(ies) and are eligible for intensive therapies are offered an autologous hematopoietic cell transplant (HCT) as front-line consolidation followed by rituximab maintenance. Allogeneic HCT is an option for younger and fit patients with high-risk disease or in patients who have relapsed after autologous HCT. Read More

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Diagnostically challenging immunophenotypic shift in mantle cell lymphoma following ibrutinib and venetoclax therapy.

Pathology 2021 May 1. Epub 2021 May 1.

Department of Diagnostic Haematology, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Melbourne, Vic, Australia; Department of Medicine, The University of Melbourne, Parkville, Vic, Australia.

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Ibrutinib improves the efficacy of anti-CD19-CAR T-cell therapy in patients with refractory non-Hodgkin lymphoma.

Cancer Sci 2021 May 1. Epub 2021 May 1.

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, the Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.

The efficacy and side effects of the second-time humanized CD19 chimeric antigen receptor (CD19-CAR) T-cell therapy after unsuccessful first-time anti-CD19-CAR T-cell therapy and subsequent ibrutinib salvage treatment were observed in patients with refractory B-cell lymphoma. In our study, 3 patients with refractory mantle cell lymphoma (MCL) and 4 patients with refractory follicular lymphoma (FL) reached stable disease (SD), partial remission (PR), or progression of disease (PD) after first-time humanized anti-CD19-CAR T-cell therapy. They received ibrutinib as a salvage treatment and kept an SD in the following 7-16 mo, but their disease progressed again during ibrutinib salvage treatment. Read More

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Health Economic Aspects of Chimeric Antigen Receptor T-cell Therapies for Hematological Cancers: Present and Future.

Hemasphere 2021 Feb 28;5(2):e524. Epub 2021 Jan 28.

Erasmus School of Health Policy and Management, Erasmus University, Rotterdam, The Netherlands.

Since 2018, 2 chimeric antigen receptor (CAR) T-cell therapies received approval from the European Medicine Agency, with list prices around 320 000 Euro (€) (EUR) per treatment. These high prices raise concerns for patient access and the sustainability of healthcare systems. We aimed to estimate the costs and budget impact associated with CAR T-cell therapies for current and future indications in hematological cancers from 2019 to 2029. Read More

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February 2021

Novel antigens of CAR T cell therapy: New roads; old destination.

Transl Oncol 2021 Jul 13;14(7):101079. Epub 2021 Apr 13.

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Research and Development Center of Biotechnology, Tarbiat Modares University, Tehran, Iran. Electronic address:

Chimeric antigen receptor T cell (CAR-T) therapy has so far proved itself as a reliable therapeutic option for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and mantle cell lymphoma (MCL). However, this picture is not as colorful when it comes to the treatment of solid tumors mainly due to the lack of definitive tumor antigens, as well as the immunosuppressive tumor microenvironments and poor CAR-T infiltration. The recent developments in bioinformatics and cell biology, such as single-cell RNA sequencing, have offered silver linings in the subject of tumor antigen discovery. Read More

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P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Drug Discovery and Design Center, The Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Read More

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Allogeneic stem cell transplantation for mantle cell lymphoma-update of the prospective trials of the East German Study Group Hematology/Oncology (OSHO#60 and #74).

Ann Hematol 2021 Jun 8;100(6):1569-1577. Epub 2021 Apr 8.

Department of Internal Medicine C - Haematology and Oncology, Stem Cell Transplantation, Palliative Care - University of Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.

Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma with an often aggressive course, incurable by chemotherapy. Consolidation with high-dose therapy and autologous stem cell transplantation (autoSCT) has a low transplant-related mortality but does not lead to a survival plateau. Allogeneic stem cell transplantation (alloSCT) is associated with a higher early mortality, but can cure MCL. Read More

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Relapsed Mantle Cell Lymphoma: Current Management, Recent Progress, and Future Directions.

J Clin Med 2021 Mar 14;10(6). Epub 2021 Mar 14.

Division of Hematology, The Ohio State University, Columbus, OH 43210, USA.

The increasing number of approved therapies for relapsed mantle cell lymphoma (MCL) provides patients effective treatment options, with increasing complexity in prioritization and sequencing of these therapies. Chemo-immunotherapy remains widely used as frontline MCL treatment with multiple targeted therapies available for relapsed disease. The Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib, and zanubrutinib achieve objective responses in the majority of patients as single agent therapy for relapsed MCL, but differ with regard to toxicity profile and dosing schedule. Read More

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CDKN1C-mediated growth inhibition by an EZH1/2 dual inhibitor overcomes resistance of mantle cell lymphoma to ibrutinib.

Cancer Sci 2021 Jun 1;112(6):2314-2324. Epub 2021 May 1.

Division of Haematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma, which is characterized by overexpression of cyclin D1. Although novel drugs, such as ibrutinib, show promising clinical outcomes, relapsed MCL often acquires drug resistance. Therefore, alternative approaches for refractory and relapsed MCL are needed. Read More

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Mantle cell lymphoma - advances in molecular biology, prognostication and treatment approaches.

Br J Haematol 2021 Mar 30. Epub 2021 Mar 30.

Department of Medicine III, LMU Hospital, Munich, Germany.

Mantle cell lymphoma (MCL) is clinically characterised by its heterogenous behaviour with courses ranging from indolent cases that do not require therapy for years to highly aggressive MCL with a very limited prognosis. A better understanding of the complex biology of MCL has already led to the approval of several innovative agents, expanding the landscape of MCL therapies and improving therapeutic options especially for refractory/relapsed (R/R) disease. Nevertheless, to further optimise MCL treatment, early identification of individual risk profile and risk-adapted, patient-tailored choice of therapeutic strategy needs to be prospectively incorporated into clinical patient management. Read More

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Novel Treatments for Mantle Cell Lymphoma: From Targeted Therapies to CAR T Cells.

Drugs 2021 Apr 30;81(6):669-684. Epub 2021 Mar 30.

James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.

Mantle cell lymphoma is a rare B-cell non-Hodgkin's lymphoma that retains a sobering prognosis despite an extensive research effort. Mantle cell lymphoma remains incurable even with aggressive, and at times toxic, chemoimmunotherapy with early incorporation of autologous stem cell transplantation. Given this, attention has turned to the use of targeted therapies addressing dysregulation of B-cell signaling pathways. Read More

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Chimeric Antigen Receptor T Cells for B-Cell Lymphoma.

Cancer J 2021 Mar-Apr 01;27(2):107-111

From the Dana Farber Cancer Institute, Boston, MA.

Abstract: Anti-CD19-directed chimeric antigen receptor (CAR) T-cell therapy yields durable remissions in up to 40% of patients with chemoresistant aggressive B-cell non-Hodgkin lymphoma (NHL), a group of patients expected only to survive on average 6 months. Although longer follow-up is needed to define durability, CD19 CAR T cells are demonstrating similar promise in other B-NHL subtypes such as mantle cell lymphoma and the indolent B-cell NHLs. This transformative therapy, however, remains hamstrung by its associated toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as by mechanisms of resistance and relapse and accessibility. Read More

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BAFF receptor antibody for mantle cell lymphoma therapy.

Oncoimmunology 2021 Mar 5;10(1):1893501. Epub 2021 Mar 5.

Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.

Mantle cell lymphoma (MCL) is an aggressive form of B cell non-Hodgkin's lymphoma and remains incurable under current treatment modalities. One of the main reasons for treatment failure is the development of drug resistance. Accumulating evidence suggests that B cell activating factor (BAFF) and BAFF receptor (BAFF-R) play an important role in the proliferation and survival of malignant B cells. Read More

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R-MACLO-IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma - Long term follow up results.

Am J Hematol 2021 06 7;96(6):680-689. Epub 2021 Apr 7.

Department of Medicine, Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.

We present long-term combined results of two clinical trials implementing R-MACLO-IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM-MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM-MCL2 ClinicalTrials. Read More

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Clinical characteristics of patients with B-cell lymphoma enrolled in clinical trials for aggressive lymphoma in Japan: Japan Clinical Oncology Group - Lymphoma Study Group study - JCOG0108A.

J Clin Exp Hematop 2021 ;61(1):35-41

National Cancer Center Hospital, Tokyo, Japan.

The clinical characteristics of B-cell lymphoma (BCL) were studied through the combined analysis of six clinical trials conducted by the Japan Clinical Oncology Group - Lymphoma Study Group (JCOG-LSG) for aggressive lymphoma in the 1990s, before the introduction of rituximab. Through a central pathological review, 829 patients were diagnosed with BCL according to the World Health Organization classification and treated with doxorubicin-containing combination chemotherapies. Of these patients, 642, 104, 30, and 24 patients were diagnosed with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL), respectively. Read More

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Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma.

Cell Rep 2021 Mar;34(11):108870

Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address:

Ibrutinib, a bruton's tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Read More

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