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Current Oncology
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New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple...
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New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 23423

Special Issue Editors

Prof. Dr. Marie-Christine Kyrtsonis

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Guest Editor
Hematology Section of the 1st Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens’ Medical School, Laikon Hospital, 11527 Athens, Greece
Interests: multiple myeloma; Waldenstrom's macroglobulinemia; lymphomas; leukemias; myeloproliferative disorders; myelodysplastic syndromes; prognosis; microenvironment; cytokines
Prof. Dr. Meletios-Athanasios Dimopoulos

grade E-Mail Website
Co-Guest Editor
Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, 80 Vas. Sofias Ave, 11528 Athens, Greece
Interests: multiple myeloma; Waldenstrom’s macroglobulinemia; amyloidosis; lymphomas; oncology
Dr. Emmanouil Spanoudakis

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Co-Guest Editor
Department of Internal Medicine, Alexandroupolis University Hospital, Democritus University of Thrace’s Medical School, Alexandroupolis, Greece
Interests: multiple myeloma; Waldenstrom’s macroglobulinemia; amyloidosis; lymphomas; oncology

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is a plasmacytic dyscrasia characterized by monoclonal paraprotein-secreting plasma cells, proliferating in the bone marrow, and accompanied by morbid manifestations such as bone pains with eventual spontaneous fractures, anemia, renal failure, possible hypercalcemia, and frequent febrile infection. The disease course is punctuated by remissions followed by relapses.

Increasing knowledge about myeloma underlining biology along with technology improvements have led to an unbelievable treatment evolution for the benefit of most patients. Likewise, with the introduction of proteasome inhibitors and IMiDs that became the basis of most therapeutic schemas, coupled with monoclonal antibodies and other new agents, the duration of responses and overall survival have been substantially prolonged, and the quality of life improved. Meanwhile, newer modalities are emerging, and some are already available, allowing the most promising ones to potentially cure for some of our patients.

Over recent years, diagnostic procedures and risk stratification strategies have adapted to the new state of management and have been improved. However, due to the emergence of aggressive myeloma sub-clones and unknown biologic processes, the disease ultimately escapes treatment control and becomes lethal. Therefore, a lot remains to be studied, evaluated, and assessed in order to reach optimal effect.

We would like to invite physicians and researchers involved in this field to contribute to this Special Issue with their observations and results.

Prof. Dr. Marie-Christine Kyrtsonis
Prof. Dr. Meletios-Athanasios Dimopoulos
Dr. Emmanouil Spanoudakis
Guest Editors

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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. Current Oncology is an international peer-reviewed open access monthly 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 2200 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
  • diagnosis procedures
  • prognosis
  • treatment
  • biology
  • prognostic factors
  • pathophysiology

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Published Papers (7 papers)

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Research

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17 pages, 5240 KiB  
Article
Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma
by Jian Wu, Shengjun Fan, Daniel Feinberg, Xiaobei Wang, Shaima Jabbar and Yubin Kang
Curr. Oncol. 2023, 30(3), 3047-3063; https://doi.org/10.3390/curroncol30030231 - 4 Mar 2023
Cited by 4 | Viewed by 2762
Abstract
Mitophagy plays an important role in maintaining mitochondrial homeostasis by clearing damaged mitochondria. Sphingosine kinase 2 (SK2), a type of sphingosine kinase, is an important metabolic enzyme involved in generating sphingosine-1-phosphate. Its expression level is elevated in many cancers and is associated with [...] Read more.
Mitophagy plays an important role in maintaining mitochondrial homeostasis by clearing damaged mitochondria. Sphingosine kinase 2 (SK2), a type of sphingosine kinase, is an important metabolic enzyme involved in generating sphingosine-1-phosphate. Its expression level is elevated in many cancers and is associated with poor clinical outcomes. However, the relationship between SK2 and mitochondrial dysfunction remains unclear. We found that the genetic downregulation of SK2 or treatment with ABC294640, a specific inhibitor of SK2, induced mitophagy and apoptosis in multiple myeloma cell lines. We showed that mitophagy correlates with apoptosis induction and likely occurs through the SET/PP2AC/PARK2 pathway, where inhibiting PP2AC activity may rescue this process. Furthermore, we found that PP2AC and PARK2 form a complex, suggesting that they might regulate mitophagy through protein–protein interactions. Our study demonstrates the important role of SK2 in regulating mitophagy and provides new insights into the mechanism of mitophagy in multiple myeloma. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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12 pages, 771 KiB  
Article
Assessing Pretransplant and Posttransplant Therapy Response in Multiple Myeloma Patients
by Cristina Potre, Ema Borsi, Ovidiu Potre, Miruna Samfireag, Dan Costachescu, Bianca Cerbu, Felix Bratosin, Cristina Secosan and Rodica Anamaria Negrean
Curr. Oncol. 2022, 29(11), 8501-8512; https://doi.org/10.3390/curroncol29110670 - 8 Nov 2022
Viewed by 2973
Abstract
Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a [...] Read more.
Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27–42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20–73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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9 pages, 939 KiB  
Article
Spinal Lesions as Clinical Manifestations of Plasma Cell Neoplasia
by Lea Baumgart, Melanie Barz, Claire Delbridge, Amir Kaywan Aftahy, Insa Katrin Janssen, Philipp J. Jost, Yu-Mi Ryang, Bernhard Meyer and Jens Gempt
Curr. Oncol. 2022, 29(9), 6236-6244; https://doi.org/10.3390/curroncol29090490 - 29 Aug 2022
Cited by 4 | Viewed by 2564
Abstract
(1) Background: Plasma cell neoplasia can be separated into independent subtypes including multiple myeloma (MM) and solitary plasmacytoma of the bone (SBP). The first clinical signs patients present with are skeletal pain, most commonly involving ribs and vertebrae. (2) Methods: Retrospective analysis of [...] Read more.
(1) Background: Plasma cell neoplasia can be separated into independent subtypes including multiple myeloma (MM) and solitary plasmacytoma of the bone (SBP). The first clinical signs patients present with are skeletal pain, most commonly involving ribs and vertebrae. (2) Methods: Retrospective analysis of 114 patients (38 female, 76 male) receiving spinal surgery from March 2006 until April 2020. Neurological impairments and surgical instability were the criteria for intervention in this cohort. Analysis was based on demographic data, Spinal Instability Neoplastic Score (SINS), location of the lesion, spinal levels of tumor involvement, surgical treatment, histopathological workup, adjuvant therapy, functional outcome, and overall survival (OS). (3) Results: The following surgical procedures were performed: posterior stabilization only in 9 patients, posterior stabilization and decompression without vertebral body replacement in 56 patients, tumor debulking and decompression only in 8 patients, anterior approach in combined approach without vertebral body replacement and without biopsy and/or without kyphoplasty in 33 patients, 3 patients received biopsies only, and 5 patients received kyphoplasty only. The histopathology diagnoses were MM in 94 cases and SBP in 20 cases. Median OS was 72 months (53.4–90.6 months). Preoperative KPSS was 80% (range 40–100%), the postoperative KPSS was 80% (range 50–100%). (4) Conclusions: Surgery for patients with plasma cell neoplasia is beneficial in case of neurological impairment and spinal instability. Moreover, we were able to show that patients with MM and a low number of spinal levels to be supplied have a better prognosis as well as a younger age at the time of the surgical intervention. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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Review

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23 pages, 1075 KiB  
Review
Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management
by Mariam Markouli, Fauzia Ullah, Serhan Unlu, Najiullah Omar, Nerea Lopetegui-Lia, Marissa Duco, Faiz Anwer, Shahzad Raza and Danai Dima
Curr. Oncol. 2023, 30(7), 6330-6352; https://doi.org/10.3390/curroncol30070467 - 1 Jul 2023
Cited by 22 | Viewed by 4598
Abstract
Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric [...] Read more.
Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, has radically shifted the treatment paradigm. However, despite the promising potential of these therapies for broader application, frequent and significant adverse effects have been reported, both in short- and in long-term settings, requiring increasing awareness and vigilance in the treating team, close monitoring, and prompt interventions with a multidisciplinary approach. In this review, we will discuss the toxicities associated with CAR-T cell and bispecific antibody therapies, focusing on results from major clinical studies and real-world observations. In addition, we will emphasize on effective strategies for prevention, monitoring and management, and provide expert recommendations. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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23 pages, 797 KiB  
Review
Tumor-Associated Macrophages in Multiple Myeloma: Key Role in Disease Biology and Potential Therapeutic Implications
by Emanuele Cencini, Anna Sicuranza, Sara Ciofini, Alberto Fabbri, Monica Bocchia and Alessandro Gozzetti
Curr. Oncol. 2023, 30(7), 6111-6133; https://doi.org/10.3390/curroncol30070455 - 25 Jun 2023
Cited by 13 | Viewed by 3443
Abstract
Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk [...] Read more.
Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk between these cells and the MM tumor cells. Tumor-associated macrophages (TAM) have an important role in the MM pathogenesis, since they could promote plasma cells proliferation and angiogenesis, further supporting MM immune evasion and progression. TAM are polarized towards M1 (classically activated, antitumor activity) and M2 (alternatively activated, pro-tumor activity) subtypes. Many studies demonstrated a correlation between TAM, disease progression, drug-resistance and reduced survival in lymphoproliferative neoplasms, including MM. MM plasma cells in vitro could favor an M2 TAM polarization. Moreover, a possible correlation between the pro-tumor effect of M2 TAM and a reduced sensitivity to proteasome inhibitors and immunomodulatory drugs was hypothesized. Several clinical studies confirmed CD68/CD163 double-positive M2 TAM were associated with increased microvessel density, chemoresistance and reduced survival, independently of the MM stage. This review provided an overview of the biology and clinical relevance of TAM in MM, as well as a comprehensive evaluation of a potential TAM-targeted immunotherapy. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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13 pages, 977 KiB  
Review
Young Myeloma Patients: A Systematic Review of Manifestations and Outcomes
by Mégane Tanguay, Christophe Dagenais, Richard LeBlanc, Imran Ahmad, Jean-Sébastien Claveau and Jean Roy
Curr. Oncol. 2023, 30(6), 5214-5226; https://doi.org/10.3390/curroncol30060396 - 23 May 2023
Cited by 12 | Viewed by 3374
Abstract
Multiple myeloma usually affects older adults. However, younger patients constitute a significant subset as approximately 10% of cases occur in subjects younger than 50 years old. Young patients, who are underrepresented in the literature, are diagnosed during their most productive years of life, [...] Read more.
Multiple myeloma usually affects older adults. However, younger patients constitute a significant subset as approximately 10% of cases occur in subjects younger than 50 years old. Young patients, who are underrepresented in the literature, are diagnosed during their most productive years of life, urging the need for tailored treatment approaches. This literature review aims to report recent studies specifically addressing young patients with a focus on characteristics at diagnosis, cytogenetics, treatments, and outcomes. We searched PubMed for studies involving young patients with multiple myeloma ≤50 years old. The time span of our literature review search was from 1 January 2010 to 31 December 2022. Overall, 16 retrospective studies were analyzed for this review. Young patients with multiple myeloma tend to have less advanced disease, more frequent light chain subtypes, and survive longer compared to their older counterparts. However, available studies included a limited number of patients; the newest revised international staging system was not used to stratify patients, cytogenetics varied from one cohort to another, and most patients did not receive contemporary triplet/quadruplet treatments. This review emphasizes the need to perform contemporary, large-scale retrospective studies to improve knowledge regarding the presentation and outcomes of young myeloma patients in the era of modern treatments. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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15 pages, 1266 KiB  
Review
Identification and Targeting of Mutant Neoantigens in Multiple Myeloma Treatment
by Valentina Urzì Brancati, Letteria Minutoli, Herbert Ryan Marini, Domenico Puzzolo and Alessandro Allegra
Curr. Oncol. 2023, 30(5), 4603-4617; https://doi.org/10.3390/curroncol30050348 - 29 Apr 2023
Cited by 1 | Viewed by 2605
Abstract
Multiple myeloma (MM) is malignant disease characterized by the clonal proliferation of plasma cells in the bone marrow, leading to anemia, immunosuppression, and other symptoms, that is generally hard to treat. In MM, the immune system is likely exposed to neoplasia-associated neoantigens for [...] Read more.
Multiple myeloma (MM) is malignant disease characterized by the clonal proliferation of plasma cells in the bone marrow, leading to anemia, immunosuppression, and other symptoms, that is generally hard to treat. In MM, the immune system is likely exposed to neoplasia-associated neoantigens for several years before the tumor onset. Different types of neoantigens have been identified. Public or shared neoantigens derive from tumor-specific modifications often reported in several patients or across diverse tumors. They are intriguing therapeutic targets because they are frequently observed, and they have an oncogenic effect. Only a small number of public neoantigens have been recognized. Most of the neoantigens that have been identified are patient-specific or “private”, necessitating a personalized approach for adaptive cell treatment. It was demonstrated that the targeting of a single greatly immunogenic neoantigen may be appropriate for tumor control. The purpose of this review was to analyze the neoantigens present in patients with MM, and to evaluate the possibility of using their presence as a prognostic factor or as a therapeutic target. We reviewed the most recent literature on neoantigen treatment strategies and on the use of bispecific, trispecific, and conjugated antibodies for the treatment of MM. Finally, a section was dedicated to the use of CAR-T in relapsed and refractory patients. Full article
(This article belongs to the Special Issue New Frontiers in Pathogenesis, Diagnosis, Prognosis and Treatment for Multiple Myeloma)
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