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Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma
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Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 17339

Special Issue Editors

Dr. Massimo Offidani

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Guest Editor
AOU delle Marche, 60126 Torrette (AN), Italy
Interests: multiple myeloma; monoclonal gammapathy; immunotherapy; transplant
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Teresa Petrucci

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Guest Editor
Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy
Interests: multiple myeloma; monoclonal gammapathy; immunotherapy; transplant

Special Issue Information

Dear Colleagues,

Treatment of multiple myeloma (MM) continues to evolve year by year, and immunotherapy has now entered its therapeutic armamentarium. In particular, monoclonal antibodies (MoAbs) such as elotuzumab, daratumumab, and isatuximab in combinations with proteasome inhibitors (PI) and immunomodulatory agents (IMiDs), successfully used for relapsed-relapsed MM, have been used in frontline therapy in patients both eligible and non-eligible for transplantation. Elotuzumab in combination with lenalidomide and dexamethasone (Rd) and, subsequently, daratumumab with Rd and with bortezomib and dexamethasone (Vd) were the first to be approved for the treatment of relapsed-refractory MM (rrMM). More recently, another anti-CD38 MoAb named isatuximab was approved by the FDA in combination with pomalidomide–dexamethasone in rrMM. Daratumumab in combination with bortezomib, melphalan, and prednisone (VMP) as well as with lenalidomide and dexamethasone (Rd) has just been approved for the treatment of newly diagnosed MM not eligible for transplantation, since these regimens have been shown to definitely induce better results compared with standard therapies. In transplant-eligible patients, many trials comparing standard treatments with regimens containing elotuzumab, daratumumab, and isatuximab either are ongoing or have concluded with very encouraging results. The new frontier of immunotherapy of MM, indeed, includes bispecific and conjugated MoAbs, a very promising active area of experimental trials in rrMM patients in which preliminary results are really exciting. It is arguable that passive and active immunotherapy will make MM a chronic disease or will cure an increasing fraction of MM patients.

Dr. Massimo Offidani, Dr. Maria Teresa Petrucci
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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
  • Monoclonal antibodies
  • Immunotherapy

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Published Papers (5 papers)

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Editorial

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6 pages, 197 KiB  
Editorial
Introduction to “Immunotherapies for Multiple Myeloma”
by Massimo Offidani and Maria Teresa Petrucci
Pharmaceuticals 2020, 13(11), 396; https://doi.org/10.3390/ph13110396 - 17 Nov 2020
Cited by 4 | Viewed by 2091
Abstract
Multiple myeloma (MM) is the second most common hematological cancer after diffuse large B-cell lymphoma, accounting for about 10% of all blood cancers [...] Full article
(This article belongs to the Special Issue Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma)

Review

Jump to: Editorial

19 pages, 2117 KiB  
Review
Drug Conjugated and Bispecific Antibodies for Multiple Myeloma: Improving Immunotherapies off the Shelf
by Gregorio Barilà, Rita Rizzi, Renato Zambello and Pellegrino Musto
Pharmaceuticals 2021, 14(1), 40; https://doi.org/10.3390/ph14010040 - 7 Jan 2021
Cited by 9 | Viewed by 3855
Abstract
The impressive improvement of overall survival in multiple myeloma (MM) patients in the last years has been mostly related to the availability of new classes of drugs with different mechanisms of action, including proteasome inhibitors (PI), immunomodulating agents (IMiDs), and monoclonal antibodies. However, [...] Read more.
The impressive improvement of overall survival in multiple myeloma (MM) patients in the last years has been mostly related to the availability of new classes of drugs with different mechanisms of action, including proteasome inhibitors (PI), immunomodulating agents (IMiDs), and monoclonal antibodies. However, even with this increased potence of fire, MM still remains an incurable condition, due to clonal selection and evolution of neoplastic clone. This concept underlines the importance of immunotherapy as one of the most relevant tools to try to eradicate the disease. In line with this concept, active and passive immunotherapies represent the most attractive approach to this aim. Antibody-drug conjugate(s) (ADCs) and bispecific antibodies (BsAbs) include two innovative tools in order to limit neoplastic plasma cell growth or even, if used at the time of the best response, to potentially eradicate the tumoral clone. Following their promising results as single agent for advanced disease, at the recent 62nd ASH meeting, encouraging data of several combinations, particularly of ADC(s) with PI or IMiDs, have been reported, suggesting even better results for patients treated earlier. In this paper, we reviewed the characteristics, mechanism of action, and clinical data available for most relevant ADC(s) and BsAbs. Full article
(This article belongs to the Special Issue Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma)
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14 pages, 631 KiB  
Review
The Role of Monoclonal Antibodies in the First-Line Treatment of Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma
by Francesca Bonello, Mariella Grasso, Mattia D’Agostino, Ivana Celeghini, Alessia Castellino, Mario Boccadoro and Sara Bringhen
Pharmaceuticals 2021, 14(1), 20; https://doi.org/10.3390/ph14010020 - 29 Dec 2020
Cited by 8 | Viewed by 5144
Abstract
Elderly transplant-ineligible (NTE) patients represent the majority of patients affected by multiple myeloma (MM). Elderly patients are a highly heterogeneous population, with large variability in health and functional status. Thus, choosing their optimal treatment is challenging. A wide range of first-line treatments is [...] Read more.
Elderly transplant-ineligible (NTE) patients represent the majority of patients affected by multiple myeloma (MM). Elderly patients are a highly heterogeneous population, with large variability in health and functional status. Thus, choosing their optimal treatment is challenging. A wide range of first-line treatments is available, and novel-agent combinations, including monoclonal antibodies (mAbs), have recently entered clinical practice. The combination of the anti-CD38 mAb daratumumab with bortezomib, melphalan and prednisone (Dara-VMP) or lenalidomide and dexamethasone (Dara-Rd) demonstrated impressive advantages in terms of progression-free survival and minimal residual disease negativity, as compared to VMP and Rd, without safety concerns. Another anti-CD38 mAb, isatuximab, is showing encouraging results, and new isatuximab-based combinations might enter clinical practice in the future. Nevertheless, available data come from clinical trials with selected patient populations and, to date, the manageability of these regimens in real-life patients or in frail patients remains unknown. Frailty-tailored treatments, including mAbs, are under evaluation in preliminary studies. In this review, we analyze recently approved mAb-based treatments for NTE newly diagnosed MM patients and new combinations under evaluation, focusing on the efficacy and safety of these regimens and on open issues regarding the choice of therapy for elderly patients. Full article
(This article belongs to the Special Issue Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma)
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12 pages, 269 KiB  
Review
The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma
by Elena Zamagni, Paola Tacchetti, Paola Deias and Francesca Patriarca
Pharmaceuticals 2020, 13(12), 451; https://doi.org/10.3390/ph13120451 - 10 Dec 2020
Cited by 2 | Viewed by 2203
Abstract
The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of [...] Read more.
The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM. Full article
(This article belongs to the Special Issue Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma)
20 pages, 1482 KiB  
Review
Monoclonal Antibodies: Leading Actors in the Relapsed/Refractory Multiple Myeloma Treatment
by Sonia Morè, Maria Teresa Petrucci, Laura Corvatta, Francesca Fazio, Massimo Offidani and Attilio Olivieri
Pharmaceuticals 2020, 13(12), 426; https://doi.org/10.3390/ph13120426 - 27 Nov 2020
Cited by 6 | Viewed by 3471
Abstract
Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and [...] Read more.
Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and daratumumab, directed against CD38, in combination with Rd and with bortezomib and dexamethasone (Vd), have been approved for the treatment of relapsed/refractory MM (RRMM) after they demonstrated excellent efficacy. More recently, another anti-CD38 MoAb named isatuximab was approved by FDA in combination with pomalidomide-dexamethasone (Pd) in the same setting. Many phase II and III trials with regimens containing these MoAbs are ongoing, and when available, preliminary data are very encouraging. In this review we will describe the results of major clinical studies that have been conducted with elotuzumab, daratumumab and isatuximab in RRMM, focusing on phase III trials. Moreover, we will summarized the emerging MoAbs-based combinations in the RRMM landscape. Full article
(This article belongs to the Special Issue Multidrug Therapies Containing Monoclonal Antibodies for Multiple Myeloma)
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