Therapy of Hodgkin Lymphoma

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

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 18286

Special Issue Editor


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Guest Editor
Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Interests: Hodgkin lymphoma; late side effects; epidemiology; microenvironment; radiotherapy; immunotherapy

Special Issue Information

Dear Colleagues,

An era of novel therapeutics for Hodgkin lymphoma (HL) has begun, following decades of slow progress in refining conventional therapy. This Special Issue will publish work that increases knowledge of new treatments in relapsed/refractory HL and brings them into earlier lines of therapy.

Brentuximab vedotin, an anti-CD30 antibody with a cytotoxic compound, was the first agent to change the landscape for classical Hodgkin lymphoma (cHL). In most countries it is currently used in relapse but not in first-line treatment.

PD-1-inhibitors have shown superior efficacy in cHL compared to other tumors, and are used in relapse and studied in first-line treatment.

CAR-T cells targeting CD30 are studied in cHL. Early results are promising but usage needs to be defined, especially concerning autologous and allogeneic stem cell transplants.

Bispecific antibodies are evolving for cHL, but development is slower than for B-cell malignancies.

Anti-CD20 antibodies are used for nodular lymphocyte-predominant HL (NLPHL). CAR-T cells and bispecific antibodies targeting B-cells could also be an option for NLPHL.

First-line treatment is still based on chemotherapy and radiotherapy. Late toxicity remains important. Besides optimizing chemotherapy, prognostication, and treatment guidance, radiotherapy techniques are evolving. Proton therapy is the most promising, with presumably less late toxicity while retaining efficacy.

Prof. Dr. Daniel Molin
Guest Editor

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Keywords

  • Hodgkin lymphoma
  • Therapy
  • Antibody-drug conjugate
  • Immune checkpoint inhibition
  • PD-1 inhibition
  • CAR-T cells
  • Bispecific antibodies
  • Chemotherapy
  • Radiotherapy

Published Papers (5 papers)

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Research

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8 pages, 386 KiB  
Article
Brentuximab Vedotin and Pembrolizumab Combination in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Single-Centre Retrospective Analysis
by Fulvio Massaro, Nathalie Meuleman, Dominique Bron, Marie Vercruyssen and Marie Maerevoet
Cancers 2022, 14(4), 982; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14040982 - 15 Feb 2022
Cited by 6 | Viewed by 2996
Abstract
Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25–30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective [...] Read more.
Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25–30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients presenting with a high-risk, multi-refractory disease. Patients achieving a Deauville score ≤4 proceeded to ASCT consolidation. After ASCT, patients received BV as maintenance for a total of 16 administrations. We collected data from 10 patients with a median age of 30.7 years. At a median follow-up of 16.5 months, we reported a complete metabolic remission (CMR) in eight patients (80%), with seven patients (70%) directly proceeding to ASCT (the other two patients in CMR are still undergoing treatment). BV consolidation was started in six patients and completed by three patients (one ongoing, two interruption). Two patients (20%) presented a progressive disease (PD) and subsequently died, while the others are still in CMR. The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients. Full article
(This article belongs to the Special Issue Therapy of Hodgkin Lymphoma)
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Review

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21 pages, 487 KiB  
Review
Novel Salvage Therapy Options for Initial Treatment of Relapsed/Refractory Classical Hodgkin’s Lymphoma: So Many Options, How to Choose?
by Radhika Takiar and Yasmin Karimi
Cancers 2022, 14(14), 3526; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143526 - 20 Jul 2022
Cited by 2 | Viewed by 3567
Abstract
The treatment landscape for relapsed/refractory classical Hodgkin’s lymphoma (cHL) has evolved with the introduction of several novel agents. Historically, the standard of care for relapsed cHL was salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, many patients are ineligible for ASCT [...] Read more.
The treatment landscape for relapsed/refractory classical Hodgkin’s lymphoma (cHL) has evolved with the introduction of several novel agents. Historically, the standard of care for relapsed cHL was salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, many patients are ineligible for ASCT or will have poor responses to salvage chemotherapy and ASCT. Brentuximab vedotin (BV) and checkpoint inhibitors (nivolumab/pembrolizumab) were initially approved in the post-ASCT setting. However, as a result of excellent responses and durable outcomes in this setting, they are now being studied and explored in earlier lines of therapy. Additionally, these agents are also being studied for post-transplant consolidation and maintenance with promising results in improving progression-free survival. We will review current salvage therapy options involving these novel agents and provide comparisons between regimens to aid the clinician in selecting the appropriate salvage regimen for patients who progress after first-line therapy. Full article
(This article belongs to the Special Issue Therapy of Hodgkin Lymphoma)
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13 pages, 650 KiB  
Review
Updates in the Role of Checkpoint Inhibitor Immunotherapy in Classical Hodgkin’s Lymphoma
by Shazia Nakhoda, Farsha Rizwan, Aldana Vistarop and Reza Nejati
Cancers 2022, 14(12), 2936; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14122936 - 14 Jun 2022
Cited by 4 | Viewed by 2877
Abstract
Classical Hodgkin’s lymphoma is a highly curable disease, but 10–25% of patients with higher-risk disease relapse. The introduction of checkpoint inhibitors (CPIs) targeting PD-1 have changed the landscape of treatment for patients with relapsed/refractory disease to multiple lines of therapy. The depth of [...] Read more.
Classical Hodgkin’s lymphoma is a highly curable disease, but 10–25% of patients with higher-risk disease relapse. The introduction of checkpoint inhibitors (CPIs) targeting PD-1 have changed the landscape of treatment for patients with relapsed/refractory disease to multiple lines of therapy. The depth of response to CPI as a monotherapy is highest in the first relapse as salvage therapy based on outcomes reported in several phase II studies. With earlier use of CPI and brentuximab vedotin, the optimal sequencing of therapy is evolving. In this review, we will summarize clinical investigation of anti-PD-1 mAb in earlier line settings to provide insights on utilizing these agents as chemotherapy- and radiation-sparing approaches, increasing depth of response, and as part of combination regimens. Full article
(This article belongs to the Special Issue Therapy of Hodgkin Lymphoma)
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17 pages, 14347 KiB  
Review
An Update on the Pathology and Molecular Features of Hodgkin Lymphoma
by Akira Satou, Taishi Takahara and Shigeo Nakamura
Cancers 2022, 14(11), 2647; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112647 - 26 May 2022
Cited by 10 | Viewed by 4888
Abstract
Hodgkin lymphomas (HLs) are lymphoid neoplasms derived from B cells and consist histologically of large neoplastic cells known as Hodgkin and Reed–Sternberg cells and abundant reactive bystander cells. HLs include two main types, classic HL (CHL) and nodular lymphocyte predominant HL (NLPHL). Recent [...] Read more.
Hodgkin lymphomas (HLs) are lymphoid neoplasms derived from B cells and consist histologically of large neoplastic cells known as Hodgkin and Reed–Sternberg cells and abundant reactive bystander cells. HLs include two main types, classic HL (CHL) and nodular lymphocyte predominant HL (NLPHL). Recent molecular analyses have revealed that an immune evasion mechanism, particularly the PD-1/PD-L1 pathway, plays a key role in the development of CHL. Other highlighted key pathways in CHL are NF-κB and JAK/STAT. These advances have dramatically changed the treatment for CHL, particularly relapsed/refractory CHL. For example, PD-1 inhibitors are now widely used in relapsed/refractory CHL. Compared with CHL, NLPHL is more characterized by preserved B cell features. Overlapping morphological and molecular features between NLPHL and T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) have been reported, and biological continuity between these two entities has been highlighted. Some THRLBCLs are considered to represent progression from NLPHLs. With considerable new understanding becoming available from molecular studies in HLs, therapies and classification of HLs are continually evolving. This paper offers a summary of and update on the pathological and molecular features of HLs for a better understanding of the diseases. Full article
(This article belongs to the Special Issue Therapy of Hodgkin Lymphoma)
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24 pages, 1066 KiB  
Review
Brentuximab-Induced Peripheral Neurotoxicity: A Multidisciplinary Approach to Manage an Emerging Challenge in Hodgkin Lymphoma Therapy
by Roser Velasco, Eva Domingo-Domenech and Anna Sureda
Cancers 2021, 13(23), 6125; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13236125 - 05 Dec 2021
Cited by 13 | Viewed by 3171
Abstract
Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate approved to treat classical Hodgkin lymphoma (HL). BV-induced peripheral neurotoxicity (BVIN) is one of the greatest concerns for haematologists treating HL for several reasons. First, BVIN is highly frequent. Most patients receiving BV will experience [...] Read more.
Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate approved to treat classical Hodgkin lymphoma (HL). BV-induced peripheral neurotoxicity (BVIN) is one of the greatest concerns for haematologists treating HL for several reasons. First, BVIN is highly frequent. Most patients receiving BV will experience some degree of BVIN, resulting in the primary reason for dose modification or discontinuation of HL therapy. Second, BV produces sensory, motor, and/or autonomic peripheral nerve dysfunction, which can present as severe, disabling forms of BVIN—predominantly motor—in some patients. Third, although largely reversible, BVIN may persist months or years after treatment and thereby become a major issue in HL survivorship. BVIN may, therefore, negatively affect the quality of life and work-life of often young patients with HL, in whom long-term survival is expected. Currently, the only strategy for BVIN includes dose adjustments and treatment discontinuation; however, this could interfere with LH therapy efficacy. In this setting, early recognition and adequate management of BVIN are critical in improving clinical outcomes. Careful neurologic monitoring may allow accurate diagnoses and gradation of ongoing forms of BVIN presentation. This review analysed current, available data on epidemiology, pathophysiology, patient- and treatment-related risk factors, clinical and neurophysiologic phenotypes, and management in patients with HL. Furthermore, this review specifically addresses limitations posed by BVIN assessments in clinical practice and provides skills and tools to improve neurologic assessments in these patients. Integrating this neurotoxic drug in clinical practice requires a multidisciplinary approach to avoid or minimise neurotoxicity burden in survivors of HL. Full article
(This article belongs to the Special Issue Therapy of Hodgkin Lymphoma)
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