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Cancers
Special Issues
Multiple Myeloma: Diagnosis and Therapy
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Multiple Myeloma: Diagnosis and Therapy

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

Deadline for manuscript submissions: 30 September 2025 | Viewed by 798

Special Issue Editors

Dr. Yvonne A. Efebera

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Guest Editor
Division of Hematology, Blood and Marrow Transplant, OhioHealth, Columbus, OH 43214, USA
Interests: multiple myeloma; plasma cell disorders; amyloidosis; blood and marrow transplant
Special Issues, Collections and Topics in MDPI journals
Dr. Nidhi Sharma

E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH 43210, USA
Interests: hematologic disorders; blood and marrow transplant
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is a heterogenous disease characterized by the presence of abnormal clonal plasma cells. Approximately 37,000 new diagnoses are made each year. Therapies aim to reduce the malignant plasma cells in the bone marrow, which is measured in part by the level of serum monoclonal protein, serum, and urine free light chains. Current first-line therapy for newly diagnosed MM patients includes induction with triplet or quadruplet novel therapies that include anti-CD38 monoclonal antibodies (antiCD38 Mabs), immune modulators (Imids), proteasome inhibitors (PIs), and steroids; followed by autologous stem cell transplants with high-dose Melphalan in eligible patients; followed by maintenance until disease progression. In the past few years, minimal residual disease (MRD) has been used as an important prognostic tool for MM, and its status can potentially help determine the most appropriate treatment option and length of maintenance based on disease characteristics and MRD negativity. Despite improvement in progression free survival (PFS) and overall survival (OS), almost all MM patients will relapse.

Many therapeutic regimens in different combinations are available for patients with relapsed and refractory multiple myeloma, including higher generations of Imids and PIs. Chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell surface maturation antigen (BCMA) and bispecific antibodies have been approved for patients at different stages of relapse/progression from one to four prior lines of therapy. CAR-T and bispecifics are being studied in earlier lines of therapy, including as part of first-line therapy. In addition, new derivatives of immunomodulatory drugs, known as cereblon E3 ligase modulators (CELMoDs), are in phase 2 and 3 studies in relapse/refractory MM.

This Special Issue will highlight the different approaches for the treatment of multiple myeloma that advance our understanding of targeting the different pathways in multiple myeloma.

Dr. Yvonne A. Efebera
Dr. Nidhi Sharma
Guest Editors

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
  • plasma cell disorders
  • relapsed and refractory multiple myeloma
  • blood and marrow transplant

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Published Papers (1 paper)

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14 pages, 690 KB  
Article
Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15)
by Yvonne Efebera, Vera Suman, Shira Dinner, Taylor O’Donnell, Ashley Rosko, John Mckay, Peter Barth, Patrick Hagen, Saad Usmani, Paul Richardson and Jacob Laubach
Cancers 2025, 17(15), 2433; https://doi.org/10.3390/cancers17152433 - 23 Jul 2025
Viewed by 428
Abstract
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the [...] Read more.
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article
(This article belongs to the Special Issue Multiple Myeloma: Diagnosis and Therapy)
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