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Multiple Myeloma: Focus on Clinical Practice in the Era of...
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Multiple Myeloma: Focus on Clinical Practice in the Era of Molecular Analysis

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 10020

Special Issue Editors

Dr. Rafael Ríos-Tamayo

E-Mail Website
Guest Editor
Hospital Universitario Puerta de Hierro, Fundación para la Investigación Biomédica del Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Majadahonda, Spain
Interests: multiple myeloma; amyloidosis AL; monoclonal gammopathies; epidemiology; genomics; prognosis; therapy
Dr. Juan José Lahuerta

E-Mail Website
Guest Editor
1. Instituto de Investigación del Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
2. Fundación PETHEMA, 28023 Madrid, Spain
Interests: multiple myeloma; clinical trials; monoclonal gammopathies

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is a complex, heterogeneous and challenging disease. Population-based cancer registries have sharpened our knowledge on risk factors, incidence, prevalence, mortality and survival in the real-world setting. A myriad of cutting-edge clinical trials has allowed for constant progress in the outcome of patients, in terms of survival and quality of life. Consequently, clinicians witness a dizzying change in the therapy guidelines, sometimes difficult to translate to daily clinical practice. On the other hand, next-generation flow, next-generation sequencing, mass-spectrometry and multi-omics large-scale studies are deciphering the keys to the interplay between the plasma cell clone, the medullary microenvironment and the damaged immune system. A comprehensive assessment of prognosis should consider host factors (particularly, comorbidity and frailty), disease factors (remarkably, circulating tumor cells, immunoparesis, extramedullary disease and high-risk disease), staging and, last but not least, the response to therapy (especially the minimal measurable disease). Most of these evaluations are far from being standardized. Artificial intelligence is playing a critical role in helping with this increasingly multifaceted task. Both diagnostic and response criteria should be adapted to this new scenario. Further biomarkers are needed in order to achieve an accurate and timely diagnosis and prognosis assessment. Remarkably, infection remains a leading cause of morbidity and mortality in MM.

Overall, a deeper knowledge of the immune system is the basis for the current immunotherapy-based approach to therapy. Despite the impressive advancement, MM remains an incurable disease. Drug resistance is a key obstacle to find the road to cure MM. The management of relapse and refractory disease, focusing on triple or more refractory patients is a challenge, in which, again, an immunotherapy-based approach, such as new bispecific antibodies and new generations of CAR-T, is now leading the battle.

The aim of this Special Issue is to give updated insights about the previously mentioned hot topics and unmet clinical needs for this devastating disease.

Dr. Rafael Ríos-Tamayo
Dr. Juan José Lahuerta
Guest Editors

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Published Papers (4 papers)

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9 pages, 772 KiB  
Communication
Efficacy of Selinexor in Relapsed/Refractory Multiple Myeloma (RRMM) Patients with del17p and Other High-Risk Abnormalities (A Retrospective Single-Center Study)
by Hamid Ehsan, Myra Robinson, Peter M. Voorhees, Kristen Cassetta, Shanice Borden, Shebli Atrash, Manisha Bhutani, Cindy Varga, Mauricio Pineda-Roman, Reed Friend and Barry A. Paul
Life 2024, 14(3), 384; https://doi.org/10.3390/life14030384 - 14 Mar 2024
Cited by 2 | Viewed by 2171
Abstract
Selinexor (Seli) is a first-in-class, oral selective inhibitor of the nuclear export protein, exportin-1 (XPO1). Seli exhibits its antitumor effect through the blockage of XPO1, which increases nuclear retention of tumor suppressor proteins (TSPs), including p53, thereby limiting the translation of oncogenes, triggering [...] Read more.
Selinexor (Seli) is a first-in-class, oral selective inhibitor of the nuclear export protein, exportin-1 (XPO1). Seli exhibits its antitumor effect through the blockage of XPO1, which increases nuclear retention of tumor suppressor proteins (TSPs), including p53, thereby limiting the translation of oncogenes, triggering cell cycle arrest and the death of malignant cells. Multiple Myeloma (MM) patients with del17p are deficient in TP53 and have a particularly poor prognosis. Given its unique mechanism of action, we investigated whether Seli has increased efficacy in RRMM patients with del17p compared to other high-risk cytogenetics (OHRC). This is an IRB-approved observational study of RRMM patients with high-risk cytogenetics (del17p, t (4;14), t (14;16) or gain 1q) or standard-risk cytogenetics treated at the Levine Cancer Institute (LCI) with a Seli-based regimen between January 2019 and December 2022. Time-to-event endpoints (PFS, OS) were evaluated using Kaplan–Meier (KM) methods. Log-rank tests compared time-to-event endpoints between cohorts [del17p vs. OHRC vs. standard risk]. We identified 40 RRMM patients with high-risk cytogenetics, including 16 patients with del17p and 24 patients with OHRC, as well as 20 with standard-risk cytogenetics. The median age was 62.5 vs. 69 vs. 65.5 years (del17p group vs. OHRC vs. standard risk). The median prior line of therapies was five (range: 3–16) with similar rates of prior autologous stem cell transplant in all arms (68.8% vs. 62.5% vs. 70.0%). The most frequently used regimens were Seli–Pomalidomide–dexamethasone(dex) or Seli–Carfilzomib–dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. The median time to start the Seli-based regimen after initial MM diagnosis was 5.6 years for the del17p group, 4.1 years in OHRC, and 4.8 years in the standard-risk group. The median follow-up time after the start of the Seli-based regimen was 10.5 months (mos) in the del17p group, 8.4 mos in OHRC, and 10.3 mos in the standard-risk group. In the del17p group, 50% had an objective response, 41.7% in the OHRC, and 35% in the standard-risk group (p = 0.71). Depth of response was also similar across the arms (12.5% vs. 12.5% vs. 10.0% VGPR p = 0.99). The median OS was 10.9 mos in the del17p group, 10.3 mos in the OHRC, and 10.3 mos in the standard-risk group (p = 0.92). The median OS was 15.5 mos for patients who received Seli as a bridging therapy versus 9 mos for Seli use for other reasons rather than as a bridge. Overall, Seli-based regimens showed promising responses even in this heavily pretreated population. Our analysis suggests that Seli-based regimens lead to similar outcomes among RRMM patients with del17p, OHRC, and standard-risk cytogenetics. This contrasts with previously reported outcomes using combinations of novel therapies in this population, where the del17p patients often have a poorer prognosis. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response. Full article
(This article belongs to the Special Issue Multiple Myeloma: Focus on Clinical Practice in the Era of Molecular Analysis)
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9 pages, 563 KiB  
Communication
Clinical Outcomes of Patients with Multiple Myeloma after Daratumumab Failure
by Irene Zamanillo, Lucia Medina de Alba, Rodrigo Gil, Rosalia de la Puerta, Rafael Alonso, Ana Jimenez-Ubieto, Maria Teresa Cedena, Maria Calbacho, Rosa Ayala and Joaquin Martinez-Lopez
Life 2023, 13(9), 1841; https://doi.org/10.3390/life13091841 - 31 Aug 2023
Viewed by 1825
Abstract
Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, [...] Read more.
Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments. Full article
(This article belongs to the Special Issue Multiple Myeloma: Focus on Clinical Practice in the Era of Molecular Analysis)
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11 pages, 1026 KiB  
Article
AL Amyloidosis and Multiple Myeloma: A Complex Scenario in Which Cardiac Involvement Remains the Key Prognostic Factor
by Rafael Ríos-Tamayo, Isabel Krsnik, Manuel Gómez-Bueno, Pablo Garcia-Pavia, Javier Segovia-Cubero, Ana Huerta, Clara Salas, Ramona Ángeles Silvestre, Amelia Sánchez, Marta Manso, Laura Delgado, Juan José Lahuerta, Joaquín Martínez-López and Rafael F. Duarte
Life 2023, 13(7), 1518; https://doi.org/10.3390/life13071518 - 6 Jul 2023
Cited by 9 | Viewed by 2983
Abstract
Monoclonal gammopathies (MGs) are a wide range of diseases that may evolve or progress over time. Comorbidity plays a critical role in this setting. The co-occurrence of two MGs is not a rare event. The evidence on the association of systemic light chain [...] Read more.
Monoclonal gammopathies (MGs) are a wide range of diseases that may evolve or progress over time. Comorbidity plays a critical role in this setting. The co-occurrence of two MGs is not a rare event. The evidence on the association of systemic light chain (AL) amyloidosis and multiple myeloma (MM) is scarce and controversial. Herein we aim to address this topic in a large series of patients of a referral center. All consecutive AL amyloidosis patients treated at our center from January 2005 to April 2023 were prospectively enrolled in a clinical and epidemiological registry. 141 patients diagnosed with AL amyloidosis were included, of which 7 (5%) had localized whereas 134 presented with systemic disease. The heart was the most frequently affected organ (90.3%). 25 patients (18.7%) fulfilled the IMWG diagnostic criteria of MM (AL/MM). Time-dependent association between AL and MM showed that the synchronous pattern is more frequent than the appearance of a second primary malignancy. The diagnostic delay was six months (m). Patients with AL/MM had a poorer median overall survival (OS) than AL-only patients (35.5 m, CI 95% 0–88.9, vs. 52.6 m, CI 95% 16.7–88.5), but this difference was not statistically significant. The prognosis in AL is dominated by the heart involvement, which is massive in this series. In our Cox regression model, only three prognostic variables remain as independent prognostic factors: age, N-terminal pro-brain natriuretic peptide (≥8500 ng/L), and undergoing an autologous stem cell transplant, whereas left ventricular ejection fraction shows a marginal effect. More and large studies focusing on the AL/MM association are needed to uncover the characteristics and prognostic impact of this association. Full article
(This article belongs to the Special Issue Multiple Myeloma: Focus on Clinical Practice in the Era of Molecular Analysis)
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13 pages, 4489 KiB  
Systematic Review
Progression-Free Survival Efficacy in Refractory/Relapsed Multiple Myeloma among Elderly Patients: A Systematic Review
by Tung-Lung Yang, Chin Lin, Ching-Liang Ho, Tzu-Chuan Huang, Yi-Ying Wu, Hong-Jie Jhou, Po-Huang Chen and Cho-Hao Lee
Life 2023, 13(12), 2259; https://doi.org/10.3390/life13122259 - 27 Nov 2023
Cited by 4 | Viewed by 2406
Abstract
Background: Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater efficacy than traditional methods, limited research has targeted elderly patients who might be less resilient to treatments. Our study [...] Read more.
Background: Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater efficacy than traditional methods, limited research has targeted elderly patients who might be less resilient to treatments. Our study aimed to evaluate treatment efficacy for these elderly patients. Methods: We carried out a comprehensive review of the literature using a systematic approach. Initially, 4966 citations were retrieved and subsequently narrowed down to 13 eligible randomized controlled trials (RCTs) through our systematic review process from databases like Embase, PubMed, and Cochrane Library from 1 January 2000 to 31 December 2022. Evidence was collated through a frequentist network meta-analysis, using the hazard ratio (HR) for evaluation. Results: Combined therapy of daratumumab, lenalidomide, and dexamethasone (DaraLenDex) was the preferred treatment for R/R MM elderly patients. Its strengths included an HR for progression-free survival (0.15; 95% CI: 0.09–0.25) and a 96% P-score. Conclusions: Our analysis suggests that, pending more comprehensive RCTs, DaraLenDex is the treatment with the highest efficacy for R/R MM in elderly patients. Full article
(This article belongs to the Special Issue Multiple Myeloma: Focus on Clinical Practice in the Era of Molecular Analysis)
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