Precision medicine in gynecological cancer (Review).

The advent of personalized and precision medicine has revolutionized oncology and treatment of gynecological cancer. These innovative approaches tailor treatments to individual patient profiles beyond genetic markers considering environmental and lifestyle factors, thereby optimizing therapeutic efficacy and minimizing adverse effects. Precision medicine uses advanced genomic technologies such as next-generation sequencing to perform comprehensive tumor profiling.

Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled in randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative and strong association between MRD negativity odds ratios and survival hazard ratios (β_PFS = -0.20, p < 0.

Integrated Network-Based Analysis of Diseases Associated with Amyloid Deposition Through a Disease-Protein-Drug Network.

At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. For this reason, we constructed a disease-protein-drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition.

Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.

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.

Trabecular Bone Score as a Complementary Tool for the Assessment of Bone Mineral Density in Patients with Asymptomatic Monoclonal Gammopathies.

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.

VCd versus VRd in Newly Diagnosed Multiple Myeloma: Matched Real-World Analysis from the Balkan Myeloma Study Group (BMSG).

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.

ciRS-7 circular RNA overexpression in plasma cells is a promising molecular biomarker of unfavorable prognosis in multiple myeloma.

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).

A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma.

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.

Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed/refractory multiple myeloma.

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.

Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma.

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.

Characteristics and Outcomes of Patients With Relapsed/Refractory Multiple Myeloma After Exposure to Lenalidomide in First Line of Therapy: A Single Center Database Review in Greece.

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.

Early microvascular coronary endothelial dysfunction precedes pembrolizumab-induced cardiotoxicity. Preventive role of high dose of atorvastatin.

Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vitro and pembrolizumab's (Pem's) cardiotoxicity in vivo, seeking for translational prevention means. Cytotoxicity was investigated in primary cardiomyocytes and splenocytes, incubated with ipilimumab, Pem and avelumab.

An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study.

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.