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JCM
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Emerging Therapies for Multiple Myeloma
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Emerging Therapies for Multiple Myeloma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 2584

Special Issue Editor

Dr. Brea C. Lipe

E-Mail Website
Guest Editor
Department of Hematology and Oncology, University of Rochester Medical Center, Rochester, NY 14642-0001, USA
Interests: multiple myeloma; other plasma cell disorders

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is a complex hematological malignancy. The treatment of multiple myeloma has evolved rapidly in recent years with the emergence of many new drugs and new data from randomized trials. These research frontiers have brought new hope for the treatment of multiple myeloma.

This Special Issue focuses on the latest advances and trends in the treatment of multiple myeloma. We hope to contribute to a comprehensive understanding of multiple myeloma treatment by providing insight into the rationale, clinical trial results, and potential applications of emerging therapeutic approaches. The scope of this Special Issue covers a variety of emerging treatment methods, including but not limited to targeted therapy, immunotherapy, CAR-T cell therapy, new drugs, and personalized medicine.

We invite researchers in the field of multiple myeloma-related areas to submit their findings as original articles or reviews to this Special Issue.

Dr. Brea C. Lipe
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. Journal of Clinical Medicine 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 2600 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
  • immunotherapy
  • targeted therapy
  • CAR-T cell therapy
  • new drugs
  • transplant

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Research

8 pages, 412 KiB  
Communication
Focusing on Selinexor for Holding and Bridging Prior to CAR-T in Relapsed/Refractory Multiple Myeloma
by Jack Khouri, Douglas Sborov, Adriana Rossi, Thomas Martin, Trinayan Kashyap, Tomer Mark and Muhamed Baljevic
J. Clin. Med. 2025, 14(12), 4071; https://doi.org/10.3390/jcm14124071 - 9 Jun 2025
Viewed by 431
Abstract
Background: The remarkable efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy (CAR-T) has had a significant impact on treatment strategies for relapsed/refractory multiple myeloma (RRMM). However, response durability remains a concern, necessitating the optimization of CAR-T procedures. Therapies preceding CAR-T [...] Read more.
Background: The remarkable efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy (CAR-T) has had a significant impact on treatment strategies for relapsed/refractory multiple myeloma (RRMM). However, response durability remains a concern, necessitating the optimization of CAR-T procedures. Therapies preceding CAR-T therapy are crucial for disease control and preserving T-cell fitness. Methods: This review summarizes the evidence supporting the potential of selinexor-based regimens as holding or bridging therapy with preclinical research, demonstrating selinexor’s ability to foster an anti-inflammatory tumor microenvironment. Results: Selinexor enhances CD8+ T-lymphocyte and NK cell activation, re-polarizes macrophages, and inhibits immunosuppressive cells. Bone marrow samples from patients in clinical studies show that selinexor increases CD8 and granzyme B expression in T-cells. Selinexor also disrupts NK cell inhibition, enhances anti-tumor activity, and reduces pro-inflammatory cytokines. Selinexor may upregulate BCMA expression and increase myeloma cell immunogenicity. Real-world data suggests selinexor as bridging therapy does not compromise CAR-T outcomes and may even improve them. Conclusions: Overall, the evidence indicates selinexor’s potential to optimize CAR-T outcomes, warranting further investigation as a holding or bridging therapy for CAR-T. Full article
(This article belongs to the Special Issue Emerging Therapies for Multiple Myeloma)
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12 pages, 755 KiB  
Article
Impact of Prior Selinexor Exposure on Outcomes of Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: An Exploratory Analysis
by Bruno Almeida Costa, Danai Dima, Tomer Mark, Norah Layla Sadek, Stephen Ijioma, David Ray, Utkarsh Goel, George Dranitsaris, Tianxiang Sheng, Erin Moshier, Tarek H. Mouhieddine, Jack Khouri and Adriana Rossi
J. Clin. Med. 2025, 14(4), 1316; https://doi.org/10.3390/jcm14041316 - 16 Feb 2025
Cited by 1 | Viewed by 1556
Abstract
Background/Objectives: Chimeric antigen receptor T-cell therapy (CAR-T) has become a key treatment option for relapsed/refractory multiple myeloma (RRMM), but factors impairing T-cell fitness may diminish efficacy. Our exploratory analysis aimed to evaluate the impact of prior treatment with a selinexor-containing regimen on [...] Read more.
Background/Objectives: Chimeric antigen receptor T-cell therapy (CAR-T) has become a key treatment option for relapsed/refractory multiple myeloma (RRMM), but factors impairing T-cell fitness may diminish efficacy. Our exploratory analysis aimed to evaluate the impact of prior treatment with a selinexor-containing regimen on CAR-T outcomes for RRMM patients. Methods: Data for this retrospective cohort study were sourced from electronic medical records at two US academic centers. Kaplan–Meier estimates assessed duration of response (DOR), progression-free survival (PFS), and overall survival (OS), reported as medians with interquartile ranges (IQRs). Cox proportional hazards regression analyzed factors potentially associated with PFS and OS, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Among 45 patients exposed to selinexor before undergoing BCMA-directed CAR-T, median therapy line numbers for selinexor use and CAR-T were 7 and 9, respectively, with 24.4% receiving selinexor as part of bridging. At median follow-up of 68 months, median PFS and OS post CAR-T were 8.0 (IQR 3.1–39.5) and 35.9 (IQR 14.2–NR) months, respectively. Overall response rate to CAR-T was 89%, with a median DOR of 8.1 months (IQR 2.9–39.0). In our multivariable model, patients who received a selinexor-based regimen in the line of therapy preceding CAR-T showed a trend toward reduced risk of death (HR = 0.08; 95% CI 0.02–0.46) and/or disease progression (HR = 0.40; 95% CI 0.14–1.09). Conclusions: Prior selinexor exposure does not appear to compromise CAR-T outcomes in heavily pretreated RRMM, suggesting potential T-cell sparing. Our findings warrant larger, prospective studies to determine whether preemptive selinexor treatment can optimize CAR-T efficacy. Full article
(This article belongs to the Special Issue Emerging Therapies for Multiple Myeloma)
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