Publications by authors named "Meletios A Dimopoulos"

Background: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved.

Methods: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring.

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Monoclonal gammopathies, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), are conditions marked by the overproduction of specific monoclonal proteins. Patients with these conditions are known to have a higher risk of fractures compared to the general population, yet there are no established guidelines for assessing or managing their skeletal health. The Trabecular Bone Score (TBS), which can be calculated from DXA images of the lumbar spine, provides additional insights into bone microarchitecture.

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  • Castleman disease (CD) is a rare non-cancerous condition that can be unicentric or multicentric (MCD), with MCD leading to serious symptoms due to cytokine issues, particularly involving interleukin-6 (IL-6).
  • This study examined the real-world effectiveness of siltuximab, an anti-IL-6 therapy recommended for idiopathic MCD, in treating patients in Greece and Romania from 2017 to 2022.
  • Out of 48 patients treated, 71.1% had a response to the treatment, with a 3-year survival rate of 74%, but some patients experienced adverse effects like elevated liver enzymes and anxiety.
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  • Multiple myeloma is a complex type of blood cancer, and Dr. Raymond Alexanian has made significant contributions to its research and treatment over his nearly 50-year career.
  • He developed the MP (melphalan-prednisone) regimen, which became a standard treatment, and collaborated with Dr. Bart Barlogie on the VAD (vincristine, doxorubicin, and dexamethasone) regimen to improve outcomes for difficult-to-treat cases.
  • Dr. Alexanian also helped establish high-dose melphalan with autologous stem cell transplantation and evaluated new drugs like thalidomide and bortezomib, leaving a lasting impact on both patient care and the quest for a
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  • - MEDI2228 is an antibody drug conjugate designed to target B-cell maturation antigen (BCMA) and was tested in a phase 1 trial for patients with relapsed/refractory multiple myeloma after prior treatments with standard medications.
  • - The trial involved 107 patients, identifying a maximum tolerated dose of 0.14 mg/kg every three weeks, with common side effects including photophobia, rash, and thrombocytopenia; two patients experienced serious dose-limiting toxicities.
  • - Although MEDI2228 showed promising efficacy with a 56.1% objective response rate in one treatment group, ocular toxicity issues led to the decision not to pursue further development of the drug.
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Background: Bortezomib, dexamethasone and cyclophosphamide (VCd) remains a popular regimen, due to its activity and low toxicity, while bortezomib, lenalidomide and dexamethasone (VRd) is widely used in US and Europe; both are combined with anti-CD38 monoclonal antibodies but VCd and VRd have not been compared directly in adequately powered prospective trials.

Aim: We compared the outcomes of 1216 patients treated with VCd (N = 690) or VRd (N = 526) in a real-world setting.

Results: Patients treated with VCd had more often severe renal dysfunction, ISS-3 disease, hypercalcemia, elevated LDH, anemia, thrombocytopenia, poor performance while VRd-treated were older and received less often autologous transplant but more frequently maintenance but the duration of induction was similar.

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  • - The PERSEUS study analyzed the effects of adding daratumumab (D) to the standard treatment VRd (bortezomib, lenalidomide, and dexamethasone) for adults with newly diagnosed multiple myeloma to see if it could improve outcomes.
  • - Participants were divided into two groups: one receiving D-VRd initially followed by D-R maintenance, and the other receiving standard VRd followed by lenalidomide alone.
  • - After about four years, results indicated that those who received D-VRd had better treatment responses and were more likely to remain alive and disease-free compared to the VRd-only group, with side effects being consistent with expectations for both treatments.
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Several non-coding RNAs are known to be associated with the pathobiology and progression of multiple myeloma (MM). ciRS-7 (also known as CDR1-AS), a key oncogenic circular RNA (circRNA) that sponges miR-7-5p and other cancer-related microRNAs, was recently found to be downregulated in malignant plasma cells resistant to immunomodulatory drugs. Considering that various circRNAs have a strong potential as molecular biomarkers, we aimed to investigate the expression of ciRS-7 in plasma cell disorders, assess its prognostic importance in MM, and compare these findings with those of individuals with smoldering MM (SMM) and monoclonal gammopathy of unknown significance (MGUS).

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  • Kidney light chain (AL) amyloidosis can lead to serious health issues including the need for kidney replacement therapy and increased mortality risk, with better outcomes linked to significant reductions in proteinuria after treatment.
  • This study aimed to confirm how different levels of kidney response to treatment relate to patient survival, using data from 732 patients over several years.
  • Results showed that deeper kidney responses within 6 months of treatment initiation were associated with significantly lower chances of needing kidney replacement therapy after 5 years.
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  • TEMPI syndrome is a rare plasma cell disorder that affects multiple systems and is characterized by symptoms like telangiectasias, erythrocytosis, and monoclonal gammopathy.
  • A specific case study details a 73-year-old man diagnosed with TEMPI syndrome after experiencing severe renal issues and erythrocytosis, who responded positively to treatment with Dara-VCD.
  • Preliminary research indicates lower levels of certain cytokines in TEMPI patients, suggesting a possible link between cytokine deregulation and ischemic changes in the kidneys, although further investigation is needed to establish a direct connection.
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  • - Uterine leiomyosarcomas (uLMS) are common tumors in the female reproductive system, and their genetics are complex, involving the Hippo pathway, which plays a role in various cancer types through its effectors YAP1 and TAZ.
  • - A study analyzed tissue samples from 32 uLMS patients, looking at the Hippo pathway's role and its relation to clinical factors such as age, stage, and treatment outcomes.
  • - The results showed that 62.5% of patients had disrupted Hippo signaling, and this was linked to improved overall survival rates, suggesting the pathway's significance in uLMS development and prognosis.
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Twice-weekly carfilzomib (27 mg/m2) plus lenalidomide and dexamethasone (KRd27) is a standard of care in relapsed/refractory multiple myeloma (RRMM). Once-weekly carfilzomib regimens have shown clinical benefits with improved patient convenience. This open-label, phase 3, multicenter, randomized study aimed to demonstrate noninferiority of the overall response rate (ORR) for once-weekly carfilzomib (56 mg/m2) plus Rd (KRd56) vs twice-weekly KRd27 in RRMM.

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  • The DNA damage response (DDR) and mitogen-activated protein kinase (MAPK) signaling pathways are essential for the survival of living organisms, and their interactions are important for proper cellular function.
  • Abnormalities in these pathways are linked to various diseases, particularly cancer and drug resistance, highlighting the need for further research.
  • The latest findings in treating multiple myeloma focus on targeting components of the DDR and MAPK pathways, opening up opportunities for new therapeutic strategies and clinical trials.
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Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity.

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Background: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse.

Methods: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy.

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  • Cancer therapy-related cardiovascular adverse events (CAEs), especially with drugs like Carfilzomib (Cfz), are a growing concern in patients who also have comorbidities like cardiometabolic syndrome (CMS) and heart failure with reduced ejection fraction (HFrEF).
  • In experiments with mice models, it was found that Cfz did not worsen LV dysfunction in CMS but caused metabolic issues; co-administration of metformin and atorvastatin helped protect against these cardiac complications.
  • The study concludes that while CMS and HFrEF can worsen Cfz-related CAEs through metabolic and inflammatory mechanisms, metformin shows potential as a protective agent in mitigating these adverse effects.
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Background: The increasing use of lenalidomide (Len) in first-line (1L) therapy of multiple myeloma (MM) has led to a significant proportion of patients becoming Len-refractory following 1L treatment. However, there are limited real-world data on treatment strategies and outcomes of patients who become Len-refractory following 1L therapy.

Patients And Methods: This real-world retrospective cohort study analyzed Len-refractory and non-Len-refractory patients who received 1L Len and initiated second-line (2L) therapy at a Greek MM center.

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  • Advances in treating advanced and metastatic HR+/HER2-breast cancer have come from new therapies, especially the use of CDK 4/6 inhibitors combined with endocrine therapy.
  • There is still a demand for better treatments to address resistance to CDK 4/6 inhibitors and improve patient outcomes.
  • New oral selective estrogen receptor degraders (SERDs) show promise and this paper reviews clinical studies, treatment efficacy, and future research directions for these therapies.
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Once-weekly carfilzomib at 56 mg/m plus immunomodulatory drugs and dexamethasone has shown efficacy and tolerability treating early relapsed/refractory multiple myeloma (RRMM). The phase 2 SELECT study (NCT04191616) evaluated efficacy/safety of weekly carfilzomib, pomalidomide, and dexamethasone (KPd) in early RRMM patients refractory to lenalidomide. All 52 treated patients were refractory to prior treatment, and 19 (37%) were triple-class refractory.

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  • The study investigates the impact of the chemotherapy response score (CRS) on survival rates in ovarian cancer patients, comparing those who received debulking surgery to those who did not.
  • Significant differences in progression-free survival (PFS) and overall survival (OS) were found among CRS-stratified groups, with all surgical patients faring better than non-surgical ones.
  • The findings suggest that CRS is a key factor for predicting survival outcomes and could inform personalized treatment strategies for ovarian cancer patients.
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It is important to determine the risk for admission to the intensive care unit (ICU) in patients with COVID-19 presenting at the emergency department. Using artificial neural networks, we propose a new Data Ensemble Refinement Greedy Algorithm (DERGA) based on 15 easily accessible hematological indices. A database of 1596 patients with COVID-19 was used; it was divided into 1257 training datasets (80 % of the database) for training the algorithms and 339 testing datasets (20 % of the database) to check the reliability of the algorithms.

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Objectives: To report healthcare resource utilization (HCRU) and safety outcomes in systemic light chain (AL) amyloidosis from the EMN23 study.

Materials And Methods: The retrospective, observational, multinational EMN23 study included 4,480 patients initiating first-line treatment for AL amyloidosis in 2004-2018 and assessed, among other objectives, HCRU and safety outcomes. HCRU included hospitalizations, examinations, and dialysis; safety included serious adverse events (SAEs) and adverse events of special interest (AESIs).

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Waldenström macroglobulinemia (WM) is characterized by the expansion of clonal lymphoplasmacytic cells; the MYD88L265P somatic mutation is found in >90% of patients, but malignant B cells may still display intra-clonal heterogeneity. To assess clonal heterogeneity in WM, we generated and performed single-cell RNA sequencing of CD19 sorted cells from five patients with and two patients with genotype as well as two healthy donors. We identified distinct transcriptional patterns in the clonal subpopulations not only between the two genetically distinct WM subgroups but also among patients, which affected the B cell composition in the different subgroups.

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