Hodgkin Lymphoma: Present Status and Future Strategies

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

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 14176

Special Issue Editors


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Guest Editor
Department of Haematology and BMT, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: lymphoma; Hodgkin; non-Hodgkin; PET; positron emission; tomography; prognostic factors; chronic lymphocytic leukemia; lymphadenopathy

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Guest Editor
Research and Clinical Innovation Department, Antoine Lacassagne Cancer Center, Nice, France
Interests: clinical imaging; patient stratification; Hodgkin Lymphoma

Special Issue Information

Dear Colleagues,

Hodgkin Lymphoma (HL) remains unique lymphoid neoplasm with a peculiar tumoral architecture, a distinct pathobiology consisting in few neoplastic cells immortalized by a cytokine network produced by a predominant compartment of non-neoplastic cells and a favorable treatment outcome. Thanks to a great progress in understanding the disease biology, challenging and evolving treatment approaches have been proposed, leading to impressive success in long-term outcomes. As a consequence, with as much as 80% of the treated patients becoming long disease survivors, the issue of late effects of therapy has become an unmet need of particular importance.

Moving from the Ann Arbor conference held in the seventies of the past century, HL has remained the archetype for lymphoma staging and restaging procedures. In the millennium turnaround FDG-PET and later FDG-PET/CT in a single shot imaging session superseded the traditional radiological tools and became a new paradigm for lymphoma spread detection and treatment response assessment. Remarkably, the last surviving invasive tool of the surgical staging, the bone marrow trephine biopsy, proved no longer necessary in the PET era. Early chemosensitivity assessment during treatment with interim PET paved the way to PET-adapted treatment strategies in the first-line setting, in a personalized medicine approach. This treatment individualization proved able to preserve high cure rates and with less treatment-related toxicity. New PET-derived imaging tools extracted from the PET performed at baseline for staging purposes such as Metabolic Tumor Volume (MTV) and tumor Distance (Dmax) have been recently proposed for a further refinement of a personalized cancer treatment.

Despite the success of the modern chemotherapy in long-term HL control, new non-chemotherapy agents such as Brentuximab Vedotin and PD1 inhibitors have dramatically improved disease-control for relapsed/refractory cases. As in other lymphoma subsets, tumor cell DNA shed by the neoplastic cells in the bloodstream proved a very sensitive tool to monitor patients in CR to detect an impending relapse. However, the pathogenesis of HL still keeps many obscure aspects, and several clinical questions stand unsettled including optimal treatment intensity approaches, prognostic factors, especially in the era of PET/CT, and management of relapsed/refractory patients, especially in cases heavily pretreated.

We are pleased to invite you to contribute to this Special Issue of “Cancers” aiming to cover any of these different aspects of Hodgkin Lymphoma. In this Issue we welcome both original research articles and reviews. Research areas may include pathobiology, epidemiology, risk stratification and prognostic factors, treatment strategies and novel agents, PET/CT imaging, and long-term effects and toxicity.

We are looking forward to receiving your contributions.

Prof. Dr. Theodoros P. Vassilakopoulos
Prof. Dr. Andrea Gallamini
Guest Editors

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Keywords

  • Hodgkin Lymphoma
  • PET/CT
  • patient stratification
  • risk-adapted treatment
  • prognostic factors
  • radiomics
  • pathology
  • biology
  • immunotherapy

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Published Papers (4 papers)

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Research

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19 pages, 1638 KiB  
Article
Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients
by Theodoros P. Vassilakopoulos, Maria Arapaki, Panagiotis T. Diamantopoulos, Athanasios Liaskas, Fotios Panitsas, Marina P. Siakantaris, Maria Dimou, Styliani I. Kokoris, Sotirios Sachanas, Marina Belia, Chrysovalantou Chatzidimitriou, Elianna A. Konstantinou, John V. Asimakopoulos, Kyriaki Petevi, George Boutsikas, Alexandros Kanellopoulos, Alexia Piperidou, Maria-Ekaterini Lefaki, Angeliki Georgopoulou, Anastasia Kopsaftopoulou, Kalliopi Zerzi, Ioannis Drandakis, Maria N. Dimopoulou, Marie-Christine Kyrtsonis, Panayiotis Tsaftaridis, Eleni Plata, Eleni Variamis, Gerassimos Tsourouflis, Flora N. Kontopidou, Kostas Konstantopoulos, Gerassimos A. Pangalis, Panayiotis Panayiotidis and Maria K. Angelopoulouadd Show full author list remove Hide full author list
Cancers 2024, 16(2), 238; https://doi.org/10.3390/cancers16020238 - 5 Jan 2024
Cited by 1 | Viewed by 1951
Abstract
The significance of serum beta-2 microglobulin (sβ2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ2m levels were measured by a radioimmunoassay (upper [...] Read more.
The significance of serum beta-2 microglobulin (sβ2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8–3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sβ2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff (“normal versus high”). In multivariate analysis, sβ2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a “normal versus high” cutoff set at 2.4 mg/L. Full article
(This article belongs to the Special Issue Hodgkin Lymphoma: Present Status and Future Strategies)
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Review

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11 pages, 439 KiB  
Review
Treatment Strategies in Advanced-Stage Hodgkin Lymphoma
by Eldad J. Dann and René-Olivier Casasnovas
Cancers 2024, 16(11), 2059; https://doi.org/10.3390/cancers16112059 - 29 May 2024
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Abstract
The last 3 decades have witnessed a major evolution in the treatment of advanced-stage Hodgkin lymphoma (HL). The most prominent of these developments include the introduction of the international prognostic scoring (IPS) system; therapeutic decision-making based on both IPS and interim PET/CT data; [...] Read more.
The last 3 decades have witnessed a major evolution in the treatment of advanced-stage Hodgkin lymphoma (HL). The most prominent of these developments include the introduction of the international prognostic scoring (IPS) system; therapeutic decision-making based on both IPS and interim PET/CT data; the finding that a negative interim PET/CT result could be safely used for treatment de-escalation; the introduction of intensive combination chemotherapy like escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin (vincristine), procarbazine, and prednisone); and further modification of this protocol with the incorporation of a conjugated anti-CD30 antibody brentuximab vedotin (BV) into first-line regimens, like BV-AVD (BV+ adriamycin, vinblastine and dacarbazine) and BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone). The accruing data about the toxicity of the escalated BEACOPP protocol have led to decreasing the number of therapeutic cycles, substitution of toxic agents like procarbazine with dacarbazine (e.g., BEACOPDac), and reduction/omission of radiation therapy. Lately, a significant advancement has been made by the integration of checkpoint inhibitors in the first-line treatment, with preliminary results demonstrating the superiority of anti-PD1 combined with chemotherapy (nivolumab-AVD) compared to the BV-AVD regimen. This review aims to analyze recently published studies whose findings could change the treatment practice in advanced-stage HL. Full article
(This article belongs to the Special Issue Hodgkin Lymphoma: Present Status and Future Strategies)
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23 pages, 2732 KiB  
Review
Optimizing Treatment for Relapsed/Refractory Classic Hodgkin Lymphoma in the Era of Immunotherapy
by Michael P. Randall and Michael A. Spinner
Cancers 2023, 15(18), 4509; https://doi.org/10.3390/cancers15184509 - 11 Sep 2023
Cited by 5 | Viewed by 5627
Abstract
Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10–20% will relapse, and another 5–10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of [...] Read more.
Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10–20% will relapse, and another 5–10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to the management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss the management of older adults and transplant-ineligible patients, who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future. Full article
(This article belongs to the Special Issue Hodgkin Lymphoma: Present Status and Future Strategies)
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11 pages, 274 KiB  
Review
Treatment of Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Where Do We Stand? Where Do We Go?
by Dennis A. Eichenauer and Michael Fuchs
Cancers 2023, 15(13), 3310; https://doi.org/10.3390/cancers15133310 - 23 Jun 2023
Viewed by 3627
Abstract
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B cell-derived lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. In recent decades, patients with newly diagnosed NLPHL have usually been treated very similarly to classical HL (cHL). The 10-year overall survival [...] Read more.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B cell-derived lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. In recent decades, patients with newly diagnosed NLPHL have usually been treated very similarly to classical HL (cHL). The 10-year overall survival rates with HL-directed approaches are in excess of 90%. However, pathological and clinical characteristics of NLPHL resemble indolent B-cell non-Hodgkin lymphoma (B-NHL) in some aspects. Thus, nodular lymphocyte-predominant B-cell lymphoma has been proposed as an alternative name, and the use of B-NHL-directed treatment strategies has become more common in NLPHL despite limited data. Given the often indolent clinical course of NLPHL, even in the case of relapse, the majority of patients with disease recurrence do not require high-dose chemotherapy and autologous stem cell transplantation but are treated sufficiently with low-intensity approaches such as single-agent anti-CD20 antibody treatment. The establishment of novel prognostic scores for NLPHL patients may optimize risk group and treatment allocation in newly diagnosed and relapsed disease. Full article
(This article belongs to the Special Issue Hodgkin Lymphoma: Present Status and Future Strategies)
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