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Cancers
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State-of-the-Art Research on Multiple Myeloma Progression
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State-of-the-Art Research on Multiple Myeloma Progression

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

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 6943

Special Issue Editor

Dr. Shebli Atrash

E-Mail Website
Guest Editor
Levine Cancer Institute, Charlotte, NC 28204, USA
Interests: plasma cell disorders; multiple myeloma; amyloidosis; plasma cell leukemia; CAR-T
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple myeloma is a type of blood cancer that occurs when malignant plasma cells accumulate in the bone marrow. In recent years, science has made significant progress in understanding the molecular pathways involved in myeloma development and developing new drugs to treat the disease.

One crucial area of research has been the identification of genetic mutations and alterations that contribute to the development of myeloma. In addition, by studying the genomic landscape of myeloma, researchers have discovered new targets for drug development, such as inhibitors of the oncogene MYC, MDM2, IRF4, PERK, and others.

Another area of focus has been the development of immunotherapies, which harness the immune system's power to fight cancer. One promising approach has been the use of chimeric antigen receptor (CAR) T-cells or chimeric NK-cells therapy, which involves genetically engineering a donor's or patient's immune cells to recognize and attack myeloma cells and off-the-shelf bispecific T-cell engagers against multiple targets such as BCMA, GPRC5D, FcRH5, the cluster of differentiation (CD)1d and CD47, among others. In addition, the T-cell engager's underdevelopment could target multiple targets simultaneously.

Bench-to-bedside development is a vital process that enables the development of new therapies for myeloma, leading to improved patient outcomes and survival. The current state-of-the-art therapies in myeloma include immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, T-cell engagers, CAR-T cell therapies, and XPO-1 inhibitors.

The recent advances in myeloma research and drug development offer hope for improved outcomes for patients with this challenging disease.

Dr. Shebli Atrash
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 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
  • novel targets
  • novel therapies
  • molecular therapy
  • immunotherapy

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Published Papers (3 papers)

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Review

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20 pages, 330 KiB  
Review
Updates on Therapeutic Strategies in the Treatment of Relapsed/Refractory Multiple Myeloma
by Deevyashali S. Parekh, Yun Kyoung Ryu Tiger, Kevin Tony Jamouss, Justin Hassani, Maroun Bou Zerdan and Shahzad Raza
Cancers 2024, 16(17), 2931; https://doi.org/10.3390/cancers16172931 - 23 Aug 2024
Viewed by 2006
Abstract
Multiple myeloma is a heterogeneous condition characterized by the proliferation of monoclonal B-cells, for which there is currently no curative treatment available. Relapses are, unfortunately, common after first-line treatment. While the prognosis for relapsed refractory multiple myeloma is generally poor, advances in the [...] Read more.
Multiple myeloma is a heterogeneous condition characterized by the proliferation of monoclonal B-cells, for which there is currently no curative treatment available. Relapses are, unfortunately, common after first-line treatment. While the prognosis for relapsed refractory multiple myeloma is generally poor, advances in the treatment of relapsed or refractory multiple myeloma offer hope. However, the expansion of effective options in targeted treatment offers renewed optimism and hope that patients who fail on older therapies may respond to newer modalities, which are often used in combination. We review currently approved and novel investigational agents classified by mechanisms of action, efficacy, approved setting, and adverse events. We delve into future directions of treatment for relapsed/refractory multiple myeloma, reviewing novel agents and therapeutic targets for the future. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Multiple Myeloma Progression)
13 pages, 542 KiB  
Review
Immune Therapies in AL Amyloidosis—A Glimpse to the Future
by Arnon Haran, Iuliana Vaxman, Moshe E. Gatt and Eyal Lebel
Cancers 2024, 16(8), 1605; https://doi.org/10.3390/cancers16081605 - 22 Apr 2024
Cited by 1 | Viewed by 1809
Abstract
Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy [...] Read more.
Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy are gradually being evaluated and adopted in AL amyloidosis. This review explores the current state of immunotherapeutic strategies in AL amyloidosis, including monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy. We discuss the unique challenges and prospects of these therapies in AL amyloidosis, including the exposure of frail AL amyloidosis patients to immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), as well as their efficacy in promoting rapid and deep hematologic responses. Furthermore, we highlight the need for international initiatives and compassionate programs to provide access to these promising therapies and address critical unmet needs in AL amyloidosis management. Finally, we discuss future directions, including optimizing treatment sequencing and mitigating toxicities, to improve outcomes for AL amyloidosis patients. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Multiple Myeloma Progression)
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Other

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13 pages, 2148 KiB  
Systematic Review
Comparative Meta-Analysis of Triplet vs. Quadruplet Induction Regimens in Newly Diagnosed, Treatment Naïve, Multiple Myeloma
by Barry Paul, Faiz Anwer, Shahzad Raza, Aytaj Mammadzadeh, Bayan Khasawneh, Sara Shatnawi, Joseph McGuirk, Nausheen Ahmed, Zahra Mahmoudjafari, Muhammad Mushtaq, Al-Ola Abdallah and Shebli Atrash
Cancers 2024, 16(17), 2938; https://doi.org/10.3390/cancers16172938 - 23 Aug 2024
Viewed by 2519
Abstract
The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; [...] Read more.
The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Multiple Myeloma Progression)
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