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Cancers
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Novel Therapeutic Targets for the Treatment of Multiple Myeloma
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Novel Therapeutic Targets for the Treatment of Multiple Myeloma

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

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 5153

Special Issue Editor

Dr. Ilaria Saltarella

E-Mail Website
Guest Editor
Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Section of Pharmacology, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, I-70124 Bari, Italy
Interests: multiple myeloma; tumor microenvironment; angiogenesis; pharmacology; ion channels; drug resistance

Special Issue Information

Dear Colleagues,

Multiple myeloma progression and drug resistance strongly depends on the crosstalk between tumor plasma cells and the surrounding microenvironment, highlighting the importance of target tumor plasma cells and the bone marrow microenvironment. Despite the therapeutic progress, multiple myeloma is still an incurable malignancy, and many patients undergo drug resistance or relapse.

This Special Issue will focus on the recent advances in the field of multiple myeloma: novel therapeutic targets, conventional drugs, as well as innovative cell- and RNA-based therapies, with the aim of improving patient outcome and overall survival.

In this Special Issue, original research articles and reviews are welcome.

Dr. Ilaria Saltarella
Guest Editor

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. Cancers is an international peer-reviewed open access semimonthly 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 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
  • bone marrow microenvironment
  • angiogenesis
  • novel targets
  • conventional drugs
  • immunotherapy
  • RNA-based therapies
  • cell-based therapy
  • drug resistance

Published Papers (4 papers)

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Research

15 pages, 1706 KiB  
Article
Evolution of Pharmacological Treatments and Associated Costs for Multiple Myeloma in the Public Healthcare System of Catalonia: A Retrospective Observational Study
by Gemma Garrido-Alejos, Guillem Saborit-Canals, Laura Guarga, Thais de Pando, Miriam Umbria, Albert Oriol, Anna Feliu, Caridad Pontes and Antonio Vallano
Cancers 2023, 15(22), 5338; https://doi.org/10.3390/cancers15225338 - 9 Nov 2023
Viewed by 1058
Abstract
(1) Background: Our understanding of and treatment for multiple myeloma (MM) has advanced significantly, and new pharmacological treatments have promising benefits but high price tags. This study analyzes prescription patterns and pharmaceutical expenditure for MM treatments in Catalonia’s public healthcare system over eight [...] Read more.
(1) Background: Our understanding of and treatment for multiple myeloma (MM) has advanced significantly, and new pharmacological treatments have promising benefits but high price tags. This study analyzes prescription patterns and pharmaceutical expenditure for MM treatments in Catalonia’s public healthcare system over eight years. (2) Methods: A retrospective observational study examined MM treatment data from 2015 to 2022 in Catalonia, using healthcare registries from the Catalan Health Service to collect information on patients, medicines used, and treatment costs. (3) Results: A total of 4556 MM patients received treatment, with a rising trend in the number of treated patients each year from 902 in 2015 to 1899 in 2022. The mean age was 68.9 years, and patients were almost evenly distributed by gender (51.5% male). Most patients were treated with bortezomib (3338 patients), lenalidomide (2952), and/or daratumumab (1093). Most drugs showed increased utilization annually, most significantly for lenalidomide and daratumumab. The total pharmacological treatment cost throughout the entire study period was EUR 321,811,249, with lenalidomide leading with the highest total cost (EUR 157,236,784), and daratumumab exhibiting the highest increase in annual expenditure. (5) Conclusions: The study reveals a progressive increase in the number of MM patients treated and rising pharmaceutical costs. Lenalidomide and daratumumab incurred the highest costs. The findings highlight MM treatment’s economic impact and the need to monitor prescription patterns and expenditures to optimize healthcare resources and decision making. Understanding these trends can guide resource allocation effectively. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets for the Treatment of Multiple Myeloma)
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13 pages, 862 KiB  
Article
Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial
by Lisa B. Leypoldt, Maria Gavriatopoulou, Britta Besemer, Hans Salwender, Marc S. Raab, Axel Nogai, Cyrus Khandanpour, Volker Runde, Anna Jauch, Manola Zago, Peter Martus, Hartmut Goldschmidt, Carsten Bokemeyer, Meletios A. Dimopoulos and Katja C. Weisel
Cancers 2023, 15(18), 4667; https://doi.org/10.3390/cancers15184667 - 21 Sep 2023
Viewed by 1395
Abstract
Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II [...] Read more.
Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR <30 mL/min/1.73 m2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55–89) years, with a median GFR of 20.1 mL/min/1.73 m2 (interquartile range, 9.4–27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1–10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets for the Treatment of Multiple Myeloma)
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17 pages, 3100 KiB  
Article
Unlocking Drug Resistance in Multiple Myeloma: Adipocytes as Modulators of Treatment Response
by Maria Ochiai, Sara Fierstein, Farouq XsSali, Nicholas DeVito, Laura R. Purkey, Rebecca May, Abraham Correa-Medina, Mary Kelley, Thomas D. Page and Kathleen DeCicco-Skinner
Cancers 2023, 15(17), 4347; https://doi.org/10.3390/cancers15174347 - 31 Aug 2023
Cited by 1 | Viewed by 1176
Abstract
Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal proliferation of malignant plasma cells. Despite the development of a diverse array of targeted drug therapies over the last decade, patients often relapse and develop refractory disease due to multidrug resistance. [...] Read more.
Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal proliferation of malignant plasma cells. Despite the development of a diverse array of targeted drug therapies over the last decade, patients often relapse and develop refractory disease due to multidrug resistance. Obesity is a growing public health threat and a risk factor for multiple myeloma, although the mechanisms by which obesity contributes to MM growth and progression have not been fully elucidated. In the present study, we evaluated whether crosstalk between adipocytes and MM cells promoted drug resistance and whether this was amplified by obesity. Human adipose-derived stem cells (ASCs) from nineteen normal (BMI = 20–25 kg/m2), overweight (25–30 kg/m2), or obese (30–35 kg/m2) patients undergoing elective liposuction were utilized. Cells were differentiated into adipocytes, co-cultured with RPMI 8226 or U266B1 multiple myeloma cell lines, and treated with standard MM therapies, including bortezomib or a triple combination of bortezomib, dexamethasone, and lenalidomide. We found that adipocytes from overweight and obese individuals increased cell adhesion-mediated drug resistance (CAM-DR) survival signals in MM cells, and P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) drug transporter expression. Further, co-culture enhanced in vitro angiogenesis, MMP-2 activity, and protected MM cells from drug-induced decreases in viability. In summary, we provide an underlying mechanism by which obesity can impair the drug response to MM and allow for recurrence and/or disease progression. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets for the Treatment of Multiple Myeloma)
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17 pages, 2396 KiB  
Article
Lenalidomide plus Dexamethasone Combination as First-Line Oral Therapy of Multiple Myeloma Patients: A Unicentric Real-Life Study
by Vittorio Del Fabro, Mary Ann Di Giorgio, Valerio Leotta, Andrea Duminuco, Claudia Bellofiore, Uros Markovic, Alessandra Romano, Anna Bulla, Angelo Curto Pelle, Federica Elia, Francesco Di Raimondo and Concetta Conticello
Cancers 2023, 15(16), 4036; https://doi.org/10.3390/cancers15164036 - 9 Aug 2023
Cited by 1 | Viewed by 987
Abstract
Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients [...] Read more.
Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum β2-microglobulin, and creatinine clearance <30 mL/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets for the Treatment of Multiple Myeloma)
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