Latest Development in B Cell Malignancies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 12476

Special Issue Editors

Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy
Interests: chronic lymphocytic leukemia; cancer genetics; tumor microenvironment; molecular biology
Special Issues, Collections and Topics in MDPI journals
IRCCS Centro Di Riferimento Oncologico Aviano, Aviano, Italy
Interests: CLL; B cell lymphoma; tumor biology; signaling pathway; genetic alterations

Special Issue Information

Dear Colleagues,

B cell malignancies are heterogeneous in terms of genetic alterations, biological mechanisms sustaining tumor cells and, consequently, disease outcome. Over the past few years, growing interest in critical pathways has led to the discovery and design of treatment options with groundbreaking results and changes in the clinical practice, such as ibrutinib and its derivatives, or venetoclax. It is now clear that both intrinsic features of malignant B cells and the microenvironment play a pivotal role in driving and sustaining malignant B cell evolution, and that this is a two-way relationship, where tumor cells shape the bystander populations toward tolerance and support. The current challenge is to dissect and deeply characterize the biology of B cell malignancies to understand the most significant mechanism behind B cell transformation and disease progression and find targetable weak spots. This Special Issue welcomes reviews, as well as original research articles.

Dr. Francesca Arruga
Dr. Federico Pozzo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • B cell malignancies
  • target therapy
  • microenvironment
  • genetic lesions

Published Papers (5 papers)

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Research

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11 pages, 553 KiB  
Article
Evaluation of Bortezomib-BeEAM (2BeEAM) as Chemotherapy Regimen Prior to ASCT in Patients with Mantle Cell Lymphoma
by Fabrizio Huwyler, Rebekka Kunz, Ulrike Bacher, Michèle Hoffmann, Urban Novak, Michael Daskalakis, Yara Banz and Thomas Pabst
Cancers 2023, 15(7), 2091; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15072091 - 31 Mar 2023
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Abstract
(1) Background: First-line therapy in fit MCL patients may comprise high-dose chemotherapy (HDCT) with autologous transplantation to consolidate remission before maintenance treatment. However, optimization of HDCT is an unmet clinical need given the substantial relapse rate of first-line treatment, while the use of [...] Read more.
(1) Background: First-line therapy in fit MCL patients may comprise high-dose chemotherapy (HDCT) with autologous transplantation to consolidate remission before maintenance treatment. However, optimization of HDCT is an unmet clinical need given the substantial relapse rate of first-line treatment, while the use of bortezomib is a promising candidate to be added to standard HDCT. (2) Methods: We analyzed 11 consecutive patients with MCL who received bortezomib added to standard BeEAM (2BeEAM) HDCT at a single academic institution. We assessed safety, feasibility, toxicities, and survival rates. (3) Results: All patients had stage III or IV disease. We found that six patients (55%) developed new or worsening of preexisting peripheral neuropathy following administration of 2BeEAM HDCT. One patient relapsed within the first six months after HDCT, whereas three patients never reached complete remission. After a median follow-up of 22 months, the PFS was 64% and the OS 64% at the last follow-up assessment. At this time, 55% of patients were in CR. (4) Conclusions: The use of bortezomib added to standard BeEAM HDCT is associated with relevant toxicities, particularly with regards to additional neuropathy. Moreover, the anti-lymphoma efficacy of 2BeEAM HDCT appears to be modest; therefore, other therapeutic options should be evaluated for consolidation in this patient group. Full article
(This article belongs to the Special Issue Latest Development in B Cell Malignancies)
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13 pages, 774 KiB  
Article
Patients with Very High Risk of Cardiovascular Adverse Events during Carfilzomib Therapy: Prevention and Management of Events in a Single Center Experience
by Giulia Mingrone, Anna Astarita, Anna Colomba, Cinzia Catarinella, Marco Cesareo, Lorenzo Airale, Arianna Paladino, Dario Leone, Fabrizio Vallelonga, Sara Bringhen, Francesca Gay, Franco Veglio and Alberto Milan
Cancers 2023, 15(4), 1149; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15041149 - 10 Feb 2023
Cited by 1 | Viewed by 1025
Abstract
Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients but has shown cardiovascular toxicity. The risk stratification of cardiovascular adverse events (CVAEs) now seems well established, while little is known about the course and management of patients with a high-cardiovascular-risk profile or [...] Read more.
Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients but has shown cardiovascular toxicity. The risk stratification of cardiovascular adverse events (CVAEs) now seems well established, while little is known about the course and management of patients with a high-cardiovascular-risk profile or experiencing CVAEs during therapy. Therefore, we aimed to describe our experience in decision making to support health professionals in selecting the best management strategies to prevent and treat CVAEs. A total of 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We propose a novel approach, which includes advanced cardiac imaging testing for patients at high baseline CV risk to rule out clinical conditions that could contraindicate starting CFZ. After baseline evaluation, 19 (9.8%) patients were found at high risk of CVAEs: 13 (6.7%) patients underwent advanced cardiac testing and 3 (1.5%) could not receive CFZ due to CV contraindications. A total of 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial-hypertension-related events and 37 (20.8%) major CVAEs; 19 (10.7%) patients had to discontinue or modify the CFZ dosing regimen. Along with baseline risk stratification, subsequent cardiovascular clinical events and diagnostic follow-up both provided critical data to help identify conditions that could contraindicate the anticancer therapy. Full article
(This article belongs to the Special Issue Latest Development in B Cell Malignancies)
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25 pages, 4603 KiB  
Article
Evaluation of the Synergistic Potential of Simultaneous Pan- or Isoform-Specific BET and SYK Inhibition in B-Cell Lymphoma: An In Vitro Approach
by Sina Sender, Ahmad Wael Sultan, Daniel Palmer, Dirk Koczan, Anett Sekora, Julia Beck, Ekkehard Schuetz, Leila Taher, Bertram Brenig, Georg Fuellen, Christian Junghanss and Hugo Murua Escobar
Cancers 2022, 14(19), 4691; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194691 - 27 Sep 2022
Cited by 2 | Viewed by 1522
Abstract
Background: Both bromodomain and extra-terminal domain (BET) proteins and spleen tyrosine kinase (SYK) represent promising targets in diffuse large B-cell (DLBCL) and Burkitt’s lymphoma (BL). We evaluated the anti-lymphoma activity of the isoform-specific bivalent BET inhibitor AZD5153 (AZD) and the pan-BET inhibitor I-BET151 [...] Read more.
Background: Both bromodomain and extra-terminal domain (BET) proteins and spleen tyrosine kinase (SYK) represent promising targets in diffuse large B-cell (DLBCL) and Burkitt’s lymphoma (BL). We evaluated the anti-lymphoma activity of the isoform-specific bivalent BET inhibitor AZD5153 (AZD) and the pan-BET inhibitor I-BET151 (I-BET) as single agents and in combination with SYK inhibitor Entospletinib (Ento) in vitro. Methods: The effect of the single agents on cell proliferation and metabolic activity was evaluated in two DLBCL and two BL cell lines. Proliferation, metabolic activity, apoptosis, cell cycle and morphology were further investigated after a combined treatment of AZD or I-BET and Ento. RNAseq profiling of combined AZD+Ento treatment was performed in SU-DHL-4 cells. Results: Both BET inhibitors reduced cell proliferation and metabolic activity in a dose- and time-dependent manner. Combined BET and SYK inhibition enhanced the anti-proliferative effect and induced a G0/G1 cell cycle arrest. SU-DHL-4 demonstrated a pronounced modulation of gene expression by AZD, which was markedly increased by additional SYK inhibition. Functional enrichment analyses identified combination-specific GO terms related to DNA replication and cell division. Genes such as ADGRA2, MYB, TNFRSF11A, S100A10, PLEKHH3, DHRS2 and FOXP1-AS1 were identified as possible key regulators. Conclusion: Simultaneous inhibition of BET and SYK enhanced the anti-proliferative effects, and induced a combination-specific gene expression signature. Full article
(This article belongs to the Special Issue Latest Development in B Cell Malignancies)
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Review

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35 pages, 519 KiB  
Review
Current Main Topics in Multiple Myeloma
by Sonia Morè, Laura Corvatta, Valentina Maria Manieri, Attilio Olivieri and Massimo Offidani
Cancers 2023, 15(8), 2203; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082203 - 08 Apr 2023
Cited by 1 | Viewed by 4082
Abstract
Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity [...] Read more.
Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease. Full article
(This article belongs to the Special Issue Latest Development in B Cell Malignancies)
32 pages, 461 KiB  
Review
The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies
by Rafael Colmenares, Noemí Álvarez, Santiago Barrio, Joaquín Martínez-López and Rosa Ayala
Cancers 2022, 14(5), 1310; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051310 - 03 Mar 2022
Cited by 16 | Viewed by 4063
Abstract
The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising, and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing a greater utility in the diagnosis, prognosis, and response to treatment of hematological [...] Read more.
The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising, and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing a greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsies. Most of the studies about this topic have focused on B-cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for the diagnosis and minimal residual monitoring of B-cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of the early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real time. However, there are limitations, such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess the minimal residual disease, or the lack of standardization of the method, and clinical studies, to confirm its prognostic impact. This review focuses on the clinical applications of cfDNA on the minimal residual disease in hematological malignancies. Full article
(This article belongs to the Special Issue Latest Development in B Cell Malignancies)
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