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Emerging Therapies and Personalized Medicine in Lymphomas
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Emerging Therapies and Personalized Medicine in Lymphomas

A special issue of Journal of Personalized Medicine (ISSN 2075-4426).

Deadline for manuscript submissions: closed (25 December 2021) | Viewed by 34221

Special Issue Editor

Dr. Narendranath Epperla

E-Mail Website
Guest Editor
The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA
Interests: aggressive non-Hodgkin lymphomas; indolent non-Hodgkin lymphomas; Hodgkin lymphoma; Waldenstrom macroglobulinemia; targeted therapies; cellular therapies; CART
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lymphomas comprise a diverse group of hematologic malignancies, affecting patients of all ages, races, and socioeconomic statuses. Non-Hodgkin lymphomas constitute approximately 4.3% of new cancer cases in the United States, with an estimated 81,560 new cases in 2021, while Hodgkin lymphoma comprises 0.5% of all new cancer cases, with an estimated 8830 new cases in 2021. The diagnosis and classification of lymphomas require an adequate biopsy specimen and an expert pathologic review, given the different management strategies for individual lymphoma subtypes. Clinical presentation is highly heterogeneous, with the majority of lymphomas considered to be clinically aggressive.

With a better understanding of disease biology, there has been a tremendous advancement in the treatment landscape of both Hodgkin and non-Hodgkin lymphomas. The advent of small molecule-targeted therapies, antibody–drug conjugates, chimeric antigen receptor T cells (CART) and bispecific T cell engager (BITe) antibodies have revolutionized the treatment approach in the field of lymphoma, leading to improved outcomes for these patients. In this issue, we will focus on the current landscape and emerging therapies in Hodgkin and non-Hodgkin lymphomas and provide a personalized management approach for these patients in light of these advances.

Dr. Narendranath Epperla
Guest Editor

Manuscript Submission Information

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Keywords

  • aggressive non-Hodgkin lymphomas
  • indolent non-Hodgkin lymphomas
  • Hodgkin lymphoma
  • targeted therapies
  • immunotherapy
  • cellular therapies
  • CART

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Published Papers (8 papers)

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Review

14 pages, 568 KiB  
Review
Treatment of Mantle Cell Lymphoma in the Frontline Setting: Are We Ready for a Risk-Adapted Approach?
by Lindsay Hammons and Timothy S. Fenske
J. Pers. Med. 2022, 12(7), 1134; https://doi.org/10.3390/jpm12071134 - 13 Jul 2022
Cited by 1 | Viewed by 2786
Abstract
Mantle cell lymphoma (MCL), a type of B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13q32) translocation, is a clinically heterogenous disease which can range from indolent to highly aggressive. Numerous prognostic factors have been identified, including blastoid histology, the Mantle Cell Lymphoma International Prognostic [...] Read more.
Mantle cell lymphoma (MCL), a type of B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13q32) translocation, is a clinically heterogenous disease which can range from indolent to highly aggressive. Numerous prognostic factors have been identified, including blastoid histology, the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, high proliferation index, p53 deletions and/or mutations, complex karyotype, minimal residual disease, and several others. However, using these prognostic factors to guide treatment selection has largely remained elusive. Given the heterogeneous behavior of this disease and varying patient characteristics, we suggest that the time has come for a more risk-adapted approach to this disease. In this article, we review the numerous prognostic factors that have been described for MCL, both at the time of diagnosis and following first-line treatment. We then propose a risk-adapted approach to first-line therapy for MCL, which would reserve intensive therapy for the highest risk patients and spare others excessive toxicity. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
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Figure 1

16 pages, 326 KiB  
Review
Recent Advances in the Management of Relapsed and Refractory Peripheral T-Cell Lymphomas
by Zachary Braunstein, Miguel Ruiz, Walter Hanel, Polina Shindiapina, John C. Reneau and Jonathan E. Brammer
J. Pers. Med. 2022, 12(6), 964; https://doi.org/10.3390/jpm12060964 - 13 Jun 2022
Cited by 2 | Viewed by 2970
Abstract
Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous lymphomas with poor overall prognosis, particularly in the setting of relapsed/refractory PTCL. Given the limited efficacy of current therapies, several different novel therapies encompassing multiple different mechanisms of action have been evaluated for relapsed [...] Read more.
Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous lymphomas with poor overall prognosis, particularly in the setting of relapsed/refractory PTCL. Given the limited efficacy of current therapies, several different novel therapies encompassing multiple different mechanisms of action have been evaluated for relapsed and refractory PTCLs. In this review, we explore the current standard of care for relapsed/refractory PTCL, and evaluate in depth novel and emerging therapies, their scientific basis, and current trials for relapsed/refractory PTCL. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
11 pages, 268 KiB  
Review
The Use of Bruton Tyrosine Kinase Inhibitors in Waldenström’s Macroglobulinemia
by Abdullah Mohammad Khan
J. Pers. Med. 2022, 12(5), 676; https://doi.org/10.3390/jpm12050676 - 22 Apr 2022
Cited by 1 | Viewed by 2156
Abstract
Waldenström’s macroglobulinemia (WM) remains an incurable malignancy. However, a number of treatment options exist for patients with WM, including alkylating agents, anti-CD20 monoclonal antibodies, and small molecule inhibitors such as proteasome inhibitors and Bruton tyrosine kinase inhibitors (BTKi). The focus of this review [...] Read more.
Waldenström’s macroglobulinemia (WM) remains an incurable malignancy. However, a number of treatment options exist for patients with WM, including alkylating agents, anti-CD20 monoclonal antibodies, and small molecule inhibitors such as proteasome inhibitors and Bruton tyrosine kinase inhibitors (BTKi). The focus of this review is to highlight the role of BTKi in the management of WM. The first BTKi to receive US Food and Drug Administration approval for WM was ibrutinib. Ibrutinib has been extensively studied in both treatment-naïve WM patients and in those with relapsed/refractory disease. The next BTKi approved for use was zanubrutinib, and prospective data for acalabrutinib and tirabrutinib have also recently been published. Efficacy data for BTKi will be discussed, as well as the differences in their adverse event profiles. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
14 pages, 312 KiB  
Review
Relapsed/Refractory Mantle Cell Lymphoma: Beyond BTK Inhibitors
by Madelyn Burkart and Reem Karmali
J. Pers. Med. 2022, 12(3), 376; https://doi.org/10.3390/jpm12030376 - 1 Mar 2022
Cited by 14 | Viewed by 6269
Abstract
Mantle cell lymphoma (MCL) is a rare mature B-cell non-Hodgkin lymphoma (B-NHL) with historically poor outcomes. Virtually all patients will eventually experience refractory or relapsed (R/R) disease, with a virulent course of resistance and serial relapses, making treatment challenging. The available therapies for [...] Read more.
Mantle cell lymphoma (MCL) is a rare mature B-cell non-Hodgkin lymphoma (B-NHL) with historically poor outcomes. Virtually all patients will eventually experience refractory or relapsed (R/R) disease, with a virulent course of resistance and serial relapses, making treatment challenging. The available therapies for R/R MCL are not curative with conventional therapy, their goal being to palliate and prolong survival. A variety of agents approved for R/R MCL, including Bruton’s tyrosine kinase inhibitors (BTKi), changed the treatment landscape of R/R MCL. In the pre-BTKi era, the median progression-free survival (PFS) in R/R disease was 4–9 months. With the introduction of ibrutinib, the median PFS improved to 13–14.6 months. Despite these impressive results, the duration of response is limited, and resistance to BTKi inevitably develops in a subset of patients. Outcomes after progression on BTKi are extremely poor, with a median overall survival (OS) of 6 to 10 months. Certain therapies, such as chimeric antigen receptor (CAR) T cells, have shown promising results after BTKi failure. The preferred combination and sequencing of therapies beyond BTKi remain unestablished and are currently being investigated. In this review, we describe the current evidence for the available treatment of R/R MCL after progression on BTKi. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
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Graphical abstract

16 pages, 1250 KiB  
Review
Advances and Personalized Approaches in the Frontline Treatment of T-Cell Lymphomas
by Mathew G. Angelos, Hatcher J. Ballard and Stefan K. Barta
J. Pers. Med. 2022, 12(2), 267; https://doi.org/10.3390/jpm12020267 - 11 Feb 2022
Cited by 7 | Viewed by 3581
Abstract
Peripheral T-cell lymphomas (PTCLs) are a rare and heterogenous subset of non-Hodgkin lymphoma characterized by an aggressive clinical course. Historically, the treatment of PTCLs have been analogous to that of aggressive B-cell lymphomas; however, it has been well-established that overall responses and complete [...] Read more.
Peripheral T-cell lymphomas (PTCLs) are a rare and heterogenous subset of non-Hodgkin lymphoma characterized by an aggressive clinical course. Historically, the treatment of PTCLs have been analogous to that of aggressive B-cell lymphomas; however, it has been well-established that overall responses and complete remission rates are far inferior using near-identical chemotherapy strategies. Recently, there has been a plethora of newer agents designed to target distinguishing cellular and molecular features of specific PTCL subtypes. These agents have been proven to yield superior anti-lymphoma responses and, in some cases, overall survival in the relapsed, refractory, and frontline treatment setting. In this review, we will summarize and highlight the most influential clinical trials leading to the Food and Drug Administration (FDA) approval of several novel therapeutic agents against PTCL, with an emphasis on emerging studies and strategies to expand their potential use in the frontline treatment setting. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
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Figure 1

16 pages, 833 KiB  
Review
The Emerging Role of CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma
by Jeremy A. Meier, Barbara Savoldo and Natalie S. Grover
J. Pers. Med. 2022, 12(2), 197; https://doi.org/10.3390/jpm12020197 - 1 Feb 2022
Cited by 8 | Viewed by 4151
Abstract
Treatment for Hodgkin lymphoma (HL) has evolved considerably from the time it was originally described in the 19th century with many patients now being cured with frontline therapy. Despite these advances, upwards of 10% of patients experience progressive disease after initial therapy with [...] Read more.
Treatment for Hodgkin lymphoma (HL) has evolved considerably from the time it was originally described in the 19th century with many patients now being cured with frontline therapy. Despite these advances, upwards of 10% of patients experience progressive disease after initial therapy with an even higher percentage relapsing. Until recently there had been limited therapeutic options for relapsed and/or refractory HL outside of highly intensive chemotherapy with stem cell rescue. Improved understanding of the pathophysiology of HL, coupled with the emergence of more targeted therapeutics, has reshaped how we view the treatment of relapsed/refractory HL and its prognosis. With this, there has been an increased focus on immunotherapies that can reprogram the immune system to better overcome the immunosuppressive milieu found in HL for improved cancer cell killing. In particular, chimeric antigen receptor (CAR) T cells are emerging as a valuable therapeutic tool in this area. Building on the success of antibody-drug conjugates directed against CD30, CAR T cells engineered to recognize the same antigen are now reaching patients. Though still in its infancy, CAR T therapy for relapsed/refractory HL has shown exceptional promise in early-stage clinical trials with the potential for durable responses even in patients who had progressed through multiple lines of prior therapy. Here we will review currently available data on the use of CAR T cells in HL, strategies to optimize their effectiveness, and how this therapy may fit into the treatment paradigm of HL going forward. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
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Figure 1

10 pages, 252 KiB  
Review
Reappraising the Role of Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed and Refractory Hodgkin’s Lymphoma: Recent Advances and Outcomes
by Taha Al-Juhaishi, Azra Borogovac, Sami Ibrahimi, Matthew Wieduwilt and Sairah Ahmed
J. Pers. Med. 2022, 12(2), 125; https://doi.org/10.3390/jpm12020125 - 18 Jan 2022
Cited by 4 | Viewed by 3472
Abstract
Hodgkin’s lymphoma is a rare yet highly curable disease in the majority of patients treated with modern chemotherapy regimens. For patients who fail to respond to or relapse after initial systemic therapies, treatment with high-dose chemotherapy and autologous hematopoietic stem cell transplantation can [...] Read more.
Hodgkin’s lymphoma is a rare yet highly curable disease in the majority of patients treated with modern chemotherapy regimens. For patients who fail to respond to or relapse after initial systemic therapies, treatment with high-dose chemotherapy and autologous hematopoietic stem cell transplantation can provide a cure for many with chemotherapy-responsive lymphoma. Patients who relapse after autologous transplant or those with chemorefractory disease have poor prognosis and represent a high unmet need. Allogeneic hematopoietic stem cell transplantation provides a proven curative therapy for these patients and should be considered, especially in young and medically fit patients. The use of newer agents in this disease such as brentuximab vedotin and immune checkpoint inhibitors can help bring more patients to transplantation and should be considered as well. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
17 pages, 714 KiB  
Review
Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies
by Yazeed Sawalha
J. Pers. Med. 2021, 11(12), 1345; https://doi.org/10.3390/jpm11121345 - 10 Dec 2021
Cited by 24 | Viewed by 7420
Abstract
Approximately 40% of patients with diffuse large B cell lymphoma (DLBCL) do not respond or develop relapsed disease after first-line chemoimmunotherapy. A minority of these patients can be cured with autologous hematopoietic stem cell transplantation (AHCT). Although chimeric antigen receptor (CAR) T cells [...] Read more.
Approximately 40% of patients with diffuse large B cell lymphoma (DLBCL) do not respond or develop relapsed disease after first-line chemoimmunotherapy. A minority of these patients can be cured with autologous hematopoietic stem cell transplantation (AHCT). Although chimeric antigen receptor (CAR) T cells have transformed the treatment paradigm of relapsed/refractory DLBCL, only 30–40% of patients achieve durable remissions. In addition, many patients with relapsed/refractory DLBCL are ineligible to receive treatment with CAR T cells due to comorbidities or logistical limitations. Since 2019, the following four non-CAR T-cell treatments have been approved in relapsed/refractory DLBCL: polatuzumab in combination with bendamustine and rituximab, selinexor, tafasitamab plus lenalidomide, and loncastuximab. In this article, I review the data behind these four approvals and discuss important considerations on their use in clinical practice. I also review emerging therapies that have shown promising early results in relapsed/refractory DLBCL including the bispecific antibodies, antibody–drug conjugates, Bruton tyrosine kinase inhibitors, BCL2 inhibitors, immune checkpoint inhibitors, and epigenetic modifiers. Full article
(This article belongs to the Special Issue Emerging Therapies and Personalized Medicine in Lymphomas)
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