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Immunotherapy in Myeloma: A Theme Issue in Honor of Prof....
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Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton

A special issue of Hemato (ISSN 2673-6357). This special issue belongs to the section "Plasma Cell Disorders".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 24926

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Nicolaus Kröger

E-Mail Website
Guest Editor
Department of Stem Cell Transplantation, UKE, 20246 Hamburg, Germany
Interests: stem cell biology in myelofibrosis; allogeneic stem cell transplantation from unrelated donors; prevention and treatment of the donor-to-host response; cellular immunotherapy with genetically modified stem cells and T cells (CAR T cells); detection of minimal residual disease; molecular genetics in myeloid diseases; multiple myeloma; myelodysplastic syndromes
Dr. Laurent Garderet

E-Mail Website
Guest Editor
Service d'Hématologie, Hôpital Pitié Salpêtrière, 47‐83 boulevard de l'hôpital, F‐75013 Paris, France
Interests: myeloma; AL amyloidosis; monoclonal gammopathy of clinical significance; POEMS; transplantation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to honor the outstanding scientific career of Pr. Gösta Gahrton through a collection of manuscripts written by leading figures in the field of multiple myeloma immunotherapy. Thirty years ago, Pr Gahrton, along with the (EBMT) European Society for Blood and Marrow Transplantation when he was chairing the Myeloma Subcommittee of this organization, published a seminal paper reporting the outcome of allogeneic stem cell transplantation to treat multiple myeloma (N Engl J Med 1991; 325(18): 1267–73). Since then, the field of myeloma treatment, and especially the field of immune intervention, has moved dramatically. This Special Issue will cover all aspects ranging from the immunology of myeloma to different immune therapies. The immune biology of this particular bone marrow hematological malignancy will be presented. The broad spectrum of the different kinds of immune interventions, such as the allogeneic approach, the use of monoclonal antibodies including antibody–drug conjugates, and the new and very promising application of CAR T cells will also be reported on. As suggested by Pr Gahrton, immune therapy may be one step toward cure of multiple myeloma. This Special Issue will honor not only a great scientist but also a man of integrity who has been Chairman of the Nobel Committee of Karolinska Institutet.

Prof. Dr. Nicolaus Kröger
Dr. Laurent Garderet
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. Hemato is an international peer-reviewed open access quarterly 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 1000 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

  • multiple myeloma
  • the immune biology of myeloma
  • immunotherapy
  • allogeneic stem cell transplantation
  • monoclonal antibody
  • antibody–drug conjugate
  • CAR T cell
  • checkpoint inhibitor

Published Papers (7 papers)

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Editorial

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2 pages, 175 KiB  
Editorial
Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton
by Nicolaus Kröger and Laurent Garderet
Hemato 2022, 3(1), 1-2; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato3010001 - 22 Dec 2021
Viewed by 1838
Abstract
Immunotherapy has become a major pillar in the treatment of multiple myeloma [...] Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)

Review

Jump to: Editorial

12 pages, 265 KiB  
Review
Current Status of CAR-T Cell Therapy in Multiple Myeloma
by Juan Luis Reguera-Ortega, Estefanía García-Guerrero and Jose Antonio Pérez-Simón
Hemato 2021, 2(4), 660-671; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2040043 - 21 Oct 2021
Cited by 2 | Viewed by 2591
Abstract
Current data on CAR-T cell-based therapy is really promising in multiple myeloma, especially in terms of response. In heavily pretreated patients, who have already received proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, current trials report an overall response rate ranging from 81 to [...] Read more.
Current data on CAR-T cell-based therapy is really promising in multiple myeloma, especially in terms of response. In heavily pretreated patients, who have already received proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, current trials report an overall response rate ranging from 81 to 97% and 45 to 67% of complete remission rates. Data are less encouraging in terms of duration of response, although most recent trials have shown significant improvements in terms of event-free survival, with medians ranging from 8 to 14 months and up to 77% progression-free survival at 12 months with an acceptable toxicity profile. These data will be consolidated in future years and will provide new evidence on the best timing for CAR-T cell therapy. Moreover, new CAR-T designs are underway and will challenge the current results. Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)
10 pages, 260 KiB  
Review
Donor Lymphocyte Infusion to Enhance the Graft-versus-Myeloma Effect
by Nico Gagelmann and Nicolaus Kröger
Hemato 2021, 2(2), 207-216; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2020012 - 14 Apr 2021
Cited by 1 | Viewed by 2177
Abstract
Donor lymphocyte infusion (DLI) has the potential to significantly deepen the response after allogeneic stem cell transplantation (ASCT) in multiple myeloma (MM). Subsequently, DLI offers the opportunity for long-term progression-free and, most importantly, overall survival for patients with MM. DLI application is a [...] Read more.
Donor lymphocyte infusion (DLI) has the potential to significantly deepen the response after allogeneic stem cell transplantation (ASCT) in multiple myeloma (MM). Subsequently, DLI offers the opportunity for long-term progression-free and, most importantly, overall survival for patients with MM. DLI application is a complex procedure, whereby many factors need to be considered (e.g., patient-oriented factors prior to application, disease-specific factors, as well as possible combinations with further therapies during and after DLI). There are two settings in which DLI can be given, they are as follows: as a salvage option in progressive disease or in the prophylactic setting for MM patients with resolved disease to further deepen the response. While the first studies used DLI in the salvage setting, results for prophylactic DLI appear to be associated with better and prolonged outcomes. Furthermore, DLI (both prophylactic and salvage) given earlier after ASCT (3–6 months) appear to be associated with better outcomes. The incorporation of novel agents showed similar responses and survival after DLI. However, updated and larger evaluations are urgently needed to determine the specific role of multiple variables in such a complex treatment environment of ASCT in an ever-evolving field of MM. This review underlines the rationale for DLI after ASCT, results in the salvage and prophylactic settings, patterns of disease progression after DLI, as well as avenues to further enhance the graft-versus-myeloma effect exerted by DLI. Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)
15 pages, 1958 KiB  
Review
Role and Modulation of NK Cells in Multiple Myeloma
by Marie Thérèse Rubio, Adèle Dhuyser and Stéphanie Nguyen
Hemato 2021, 2(2), 167-181; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2020010 - 02 Apr 2021
Cited by 5 | Viewed by 3175
Abstract
Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regulated by a [...] Read more.
Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regulated by a balance between activating and inhibitory signals resulting from the complex interaction of surface receptors and their respective ligands. Myeloma disease evolution is associated with a progressive alteration of NK cell number, phenotype and cytotoxic functions. We review here the different therapeutic approaches that could restore or enhance NK cell functions in multiple myeloma. First, conventional treatments (immunomodulatory drugs-IMids and proteasome inhibitors) can enhance NK killing of tumor cells by modulating the expression of NK receptors and their corresponding ligands on NK and myeloma cells, respectively. Because of their ability to kill by antibody-dependent cell cytotoxicity, NK cells are important effectors involved in the efficacy of anti-myeloma monoclonal antibodies targeting the tumor antigens CD38, CS1 or BCMA. These complementary mechanisms support the more recent therapeutic combination of IMids or proteasome inhibitors to monoclonal antibodies. We finally discuss the ongoing development of new NK cell-based immunotherapies, such as ex vivo expanded killer cell immunoglobulin-like receptors (KIR)-mismatched NK cells, chimeric antigen receptors (CAR)-NK cells, check point and KIR inhibitors. Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)
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15 pages, 723 KiB  
Review
Immunotherapy with Antibodies in Multiple Myeloma: Monoclonals, Bispecifics, and Immunoconjugates
by Christie P. M. Verkleij, Wassilis S. C. Bruins, Sonja Zweegman and Niels W. C. J. van de Donk
Hemato 2021, 2(1), 116-130; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010007 - 01 Mar 2021
Cited by 3 | Viewed by 3295
Abstract
In the 2010s, immunotherapy revolutionized the treatment landscape of multiple myeloma. CD38-targeting antibodies were initially applied as monotherapy in end-stage patients, but are now also approved by EMA/FDA in combination with standards-of-care in newly diagnosed disease or in patients with early relapse. The [...] Read more.
In the 2010s, immunotherapy revolutionized the treatment landscape of multiple myeloma. CD38-targeting antibodies were initially applied as monotherapy in end-stage patients, but are now also approved by EMA/FDA in combination with standards-of-care in newly diagnosed disease or in patients with early relapse. The approved SLAMF7-targeting antibody can also be successfully combined with lenalidomide or pomalidomide in relapsed/refractory myeloma. Although this has resulted in improved clinical outcomes, there remains a high unmet need in patients who become refractory to immunomodulatory drugs, proteasome inhibitors and CD38-targeting antibodies. Several new antibody formats, such as antibody–drug conjugates (e.g., belantamab mafodotin, which was approved in 2020 and targets BCMA) and T cell redirecting bispecific antibodies (e.g., teclistamab, talquetamab, cevostamab, AMG-420, and CC-93269) are active in these triple-class refractory patients. Based on their promising efficacy, it is expected that these new antibody formats will also be combined with other agents in earlier disease settings. Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)
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14 pages, 989 KiB  
Review
Decades of Progress in Allogeneic Stem Cell Transplantation for Multiple Myeloma
by Benedetto Bruno, Giuseppe Lia, Francesca Bonifazi and Luisa Giaccone
Hemato 2021, 2(1), 89-102; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010005 - 20 Feb 2021
Cited by 1 | Viewed by 1684
Abstract
Allogeneic hematopoietic cell transplantation in multiple myeloma has evolved over the decades. Myeloablative regimens have been replaced by the reduced intensity and non-myeloablative conditionings to reduce treatment-related toxicity and mortality while sparing graft-vs.-myeloma effects. Newer agents with potent anti-myeloma activity are not mutually [...] Read more.
Allogeneic hematopoietic cell transplantation in multiple myeloma has evolved over the decades. Myeloablative regimens have been replaced by the reduced intensity and non-myeloablative conditionings to reduce treatment-related toxicity and mortality while sparing graft-vs.-myeloma effects. Newer agents with potent anti-myeloma activity are not mutually exclusive and the combination with an allograft may improve long-term outcomes in this incurable disease especially in high-risk patients. Allografting may also be a platform for other promising new cell therapies such as CAR T-cells, NK-, and CAR NK-cells. These studies are warranted in the context of clinical trials. This review highlights the progress that has been made over the decades and possible future roles of allografting in the treatment landscape of multiple myeloma Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)
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42 pages, 1338 KiB  
Review
Why Immunotherapy Fails in Multiple Myeloma
by Luis Gerardo Rodríguez-Lobato, Aina Oliver-Caldés, David F. Moreno, Carlos Fernández de Larrea and Joan Bladé
Hemato 2021, 2(1), 1-42; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010001 - 22 Dec 2020
Cited by 5 | Viewed by 8812
Abstract
Multiple myeloma remains an incurable disease despite great advances in its therapeutic landscape. Increasing evidence supports the belief that immune dysfunction plays an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts have focused on harnessing the immune system to [...] Read more.
Multiple myeloma remains an incurable disease despite great advances in its therapeutic landscape. Increasing evidence supports the belief that immune dysfunction plays an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts have focused on harnessing the immune system to exert anti-myeloma effects with encouraging outcomes. First-in-class anti-CD38 monoclonal antibody, daratumumab, now forms part of standard treatment regimens in relapsed and refractory settings and is shifting to front-line treatments. However, a non-negligible number of patients will progress and be triple refractory from the first line of treatment. Antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptors (CAR) are being developed in a heavily pretreated setting with outstanding results. Belantamab mafodotin-blmf has already received approval and other anti-B-cell maturation antigen (BCMA) therapies (CARs and bispecific antibodies are expected to be integrated in therapeutic options against myeloma soon. Nonetheless, immunotherapy faces different challenges in terms of efficacy and safety, and manufacturing and economic drawbacks associated with such a line of therapy pose additional obstacles to broadening its use. In this review, we described the most important clinical data on immunotherapeutic agents, delineated the limitations that lie in immunotherapy, and provided potential insights to overcome such issues. Full article
(This article belongs to the Special Issue Immunotherapy in Myeloma: A Theme Issue in Honor of Prof. Dr. Gösta Gahrton)
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