Publications by authors named "Meletios Athanasios Dimopoulos"

Article Synopsis
  • HER2 overexpression is a significant target for treating gynecological cancers, and Trastuzumab-Deruxtecan (T-DXd) has shown notable effectiveness against these cancers, particularly in ovarian, endometrial, and cervical malignancies.
  • A study was conducted at the Alexandra Hospital in Athens involving 10 patients with HER2-positive gynecological cancers who were treated with T-DXd, administered intravenously every 3 weeks.
  • Results indicated a median progression-free survival of 5.4 months, with 5 patients achieving a partial response, highlighting T-DXd's potential as a treatment option even for patients with prior therapies.
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Background: Isatuximab is an anti-CD38 monoclonal antibody approved for the treatment of relapsed or refractory multiple myeloma. Previous analyses of the IKEMA trial showed prolonged progression-free survival in patients with this disease who received isatuximab in combination with carfilzomib-dexamethasone as compared with those who received carfilzomib-dexamethasone alone. Herein, we report the analysis of overall survival from the IKEMA trial.

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Immunocompromised patients with hematologic diseases may experience life-threatening infections with rather uncommon manifestations. Laryngitis has been described as a potential infection in such vulnerable patients and may result in major complications, ranging from impending airway obstruction to total laryngeal necrosis. Immediate laryngoscopy is of paramount importance, as it provides quantification of laryngeal edema and evidence of necrosis.

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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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Cushing's syndrome (CS), as a result of ectopic adrenocorticotropic hormone (ACTH) production, constitutes a common paraneoplastic manifestation of various malignancies, with the most common being small cell lung carcinoma. In the literature, fewer than fifty cases associating ectopic CS with prostate cancer have been documented. In the present study, the case of a 76-year old man suffering from castration-resistant prostate adenocarcinoma that had been treated with enzalutamide and luteinizing hormone-releasing hormone (LHRH) analogue for the last four years is presented.

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Objectives: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi-centre, Phase 1, single-agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)-modified anti-CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc-gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM.

Methods: This study comprised two parts: Part-A (dose-escalation involving anti-CD38 mAb pre-treated and naïve patients) and Part-B (dose expansion).

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Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS-MM between 2000 and 2022.

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Background: Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the "readers" of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification has been identified in ovarian cancer (~18-19%) according to (TCGA) analysis.

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There is growing interest in multiple myeloma (MM) circulating tumor cells (CTCs), but their rareness in peripheral blood (PB) and inconsistency in cutoffs question their clinical utility. Herein, we applied next-generation flow cytometry in 550 bone marrow (BM) and matched PB samples to define an optimal CTC cutoff for both transplant-eligible and transplant-ineligible newly diagnosed MM (NDMM) patients. Deep phenotyping was performed to investigate unique microenvironmental features associated with CTC dissemination.

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Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

Methods: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone.

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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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Article Synopsis
  • 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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  • 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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Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA-derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM-related tRFs in ameliorating MM prognosis and risk stratification. Small RNA-seq was performed to profile tRFs in bone marrow CD138 plasma cells, revealing the significant deregulation of the mitochondrial internal tRF (mt-i-tRF) in MM versus sMM/MGUS.

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Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome's implication in the pathogenesis of hematological malignancies only recently gained attention.

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Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have unprecedentedly advanced hormone-dependent breast cancer treatment paradigm. In the metastatic setting, ribociclib has consistently demonstrated survival benefit in pre-, peri-, and postmenopausal patients, conjugating efficacy with health-related quality of life preservation. Accordingly, the emergence of cardiac and/or vascular adverse events related to this novel targeted agent is gaining significant interest.

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Aims: Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance.

Methods And Results: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year.

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Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor that has been widely used for the treatment of patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. However, in the HBV monoinfection scenario, only five cases of TDF-associated Fanconi syndrome have been reported thus far, two of them providing a confirmatory kidney biopsy.

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Article Synopsis
  • Multiple myeloma is an incurable cancer with limited treatment options for patients whose disease has returned after previous therapies; belantamab mafodotin has shown promise in early studies for these patients.
  • The DREAMM-3 phase 3 study involved 325 participants worldwide who were randomized to receive either belantamab mafodotin or a combination of pomalidomide and dexamethasone, with the main goal of evaluating progression-free survival.
  • The study is ongoing, with patients recruited between April 2020 and April 2022, and it aims to determine the safety and efficacy of belantamab mafodotin compared to traditional treatments by September 2022.
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(1) Carfilzomib (Cfz) is an antineoplastic agent indicated for the treatment of multiple myeloma. However, its beneficial action is attenuated by the occurrence of cardiotoxicity and nephrotoxicity as the most common adverse effects. Presently, there is well-established knowledge on the pathomechanisms related to these side effects; however, the research on the metabolic alterations provoked by the drug is limited.

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