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Large Cell Lymphoma: Novel Therapeutic Approaches

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 8988

Special Issue Editor


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Guest Editor
Lymphoma Unit, Department of Hematology, Institut Catalá d'Oncologia (ICO), Hospital Duran i Reynals, Univer-sitat de Barcelona, Barcelona, Spain
Interests: diffuse large B-cell lymphoma; T-cell lymphomas; mantle cell lymphoma; cutaneous lymphomas; chronic lymphocytic leukemia; post-transplant lymphoproliferative diseases; immunotherapy; targeted therapy; epidemiology; prognostic factors

Special Issue Information

Dear Colleagues,

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease. Recently, the new WHO classification updated different DLBCL subgroups. Around 60% of patients are cured with the frontline treatment R-CHOP. In the last 20 years, many efforts have been made to improve the outcome over R-CHOP without success. Recent studies combining the anti-CD79b antibody–drug conjugate polatuzumab vedotin plus R-CHP showed promising results. Salvage high-dose chemotherapy with autologous-stem-cell transplant remains the standard second-line treatment for patients who are refractory or relapse (R/R); the anti-CD19 chimeric antigen receptor T-cells (CAR-Ts) are considered the standard of care as third-line therapy, and are moving as second-line for those patients who are primary refractory or have an early relapse. Recently, new therapies have been approved for R/R DLBCL for transplant-ineligible patients, as the combinations polatuzumab plus rituximab-bendamustine and tafasitamab plus lenalidomide. Despite all these new strategies, there is still much room to improve the outcome of DLBCL patients, and new strategies are ongoing. Monoclonal antibodies such as loncastuximab, and bispecific antibodies (BsAbs) including mosunetuzumab, glofitamab, epcoritamab and odeonextamab have shown very promising results. There are also preliminary results of new tailored therapies based on molecular subtypes of DLBCL.

On the other hand, there are still unresolved situations in DLBCL, such as the identification of patients with high risk of central nervous system (CNS) progression and the use of prophylaxis, as well as the treatment of patients with proven secondary CNS infiltration.

In this Special Issue, the new WHO classification, therapies available and upcoming for both frontline and R/R settings, and the special risk situations in DLBCL will be assessed.

Prof. Dr. Eva González-Barca
Guest Editor

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Keywords

  • diffuse large B-cell lymphoma
  • molecular subtypes
  • immunotherapy
  • monoclonal antibodies
  • bispecific antibodies
  • CAR T-cells
  • targeted therapies
  • CNS infiltration

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Published Papers (3 papers)

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Review

13 pages, 270 KiB  
Review
New Insights into First-Line Therapy in Diffuse Large B-Cell Lymphoma: Are We Improving Outcomes?
by Pau Abrisqueta
J. Clin. Med. 2024, 13(7), 1929; https://doi.org/10.3390/jcm13071929 - 27 Mar 2024
Cited by 2 | Viewed by 2476
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma, comprising heterogeneous patient subgroups with distinctive biological and clinical characteristics. The R-CHOP combination (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard initial treatment, yielding prolonged remissions in over 60% [...] Read more.
Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma, comprising heterogeneous patient subgroups with distinctive biological and clinical characteristics. The R-CHOP combination (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard initial treatment, yielding prolonged remissions in over 60% of patients with advanced-stage disease. Several attempts to enhance the outcomes of this regimen over the last two decades have shown limited success. Various novel therapeutic approaches have recently emerged in lymphoma, demonstrating promising results. These include small molecules, novel monoclonal antibodies, antibody–drug conjugates (ADC), bispecific antibodies (BsAbs), and chimeric antigen receptor (CAR) T-cell therapy. This review explores recent advancements in therapeutic strategies for DLBCL and their potential impact on the initial management of DLBCL patients. Full article
(This article belongs to the Special Issue Large Cell Lymphoma: Novel Therapeutic Approaches)
15 pages, 677 KiB  
Review
Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma: New Approved Options
by Alejandro Martín García-Sancho, Almudena Cabero and Norma C. Gutiérrez
J. Clin. Med. 2024, 13(1), 70; https://doi.org/10.3390/jcm13010070 - 22 Dec 2023
Cited by 2 | Viewed by 3697
Abstract
Overall, around 40% of patients with diffuse large B-cell lymphoma (DLBCL) have refractory disease or relapse after the first line of treatment. Until relatively recently, the prognosis of patients with relapsed or refractory DLBCL was very poor and treatment options were very limited. [...] Read more.
Overall, around 40% of patients with diffuse large B-cell lymphoma (DLBCL) have refractory disease or relapse after the first line of treatment. Until relatively recently, the prognosis of patients with relapsed or refractory DLBCL was very poor and treatment options were very limited. In recent years, several novel therapies have been approved that provide more effective options than conventional chemotherapy and that have manageable toxicity profiles. CAR-T cell therapy has become the new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of the phase 3 ZUMA-7 and TRANSFORM clinical trials. This review addresses the role of CAR-T therapy and autologous stem cell transplantation in the treatment of these patients and other approved options for patients who are not candidates for transplant, such as the combinations of polatuzumab vedotin with bendamustine and rituximab, and tafasitamab with lenalidomide. Full article
(This article belongs to the Special Issue Large Cell Lymphoma: Novel Therapeutic Approaches)
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12 pages, 614 KiB  
Review
Developing New Strategies for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
by Eva Gonzalez Barca
J. Clin. Med. 2023, 12(23), 7376; https://doi.org/10.3390/jcm12237376 - 28 Nov 2023
Cited by 4 | Viewed by 2392
Abstract
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first-line chemo immunotherapy. In recent years, there have been several new therapeutic agents approved for the [...] Read more.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first-line chemo immunotherapy. In recent years, there have been several new therapeutic agents approved for the treatment of relapsed/refractory (R/R) DLBCL. These agents include anti-CD19 chimeric antigen receptor T-cell (CAR T-cell) and monoclonal antibody therapies such as polatuzumab and tafasitamab. Nevertheless, despite the high efficacy of all these new therapies, there are still patients who do not respond or relapse, representing an unmet clinical need. This review describes new promising therapies that are in clinical development to treat R/R DLBCL. Full article
(This article belongs to the Special Issue Large Cell Lymphoma: Novel Therapeutic Approaches)
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