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.

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.

The Prognostic Role of BRD4 Expression in High-Grade Serous Ovarian Cancer.

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.

Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

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.

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.

Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Background: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed.

Methods: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group).

Real-World Effectiveness and Safety of Belantamab Mafodotin Monotherapy in Triple-Class Refractory Multiple Myeloma.

B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM). The aim of this study was to assess the effectiveness and tolerability of monotherapy with the conjugated anti-BCMA monoclonal antibody belantamab mafodotin in triple-class refractory patients with MM in real-world practice. Patients refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 monoclonal antibody received belantamab mafodotin at 2.

Optimal Time Interval between Neoadjuvant Platinum-Based Chemotherapy and Interval Debulking Surgery in High-Grade Serous Ovarian Cancer.

Background: There is limited data on the optimal time interval between the last dose of neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) in high-grade serous ovarian carcinoma (HGSC).

Methods: We retrospectively identified patients with stage IIIC/IV HGSC who received NACT followed by IDS during a 15-year period (January 2003-December 2018) in our Institution.

Results: Overall, 115 patients with stage IIIC/IV HGSC were included.

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies.

Introduction: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN.

Methods: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022).

Metaplastic Carcinoma of the Breast: Case Series of a Single Institute and Review of the Literature.

Metaplastic carcinoma of the breast (MpBC) is a very rare and aggressive type of breast cancer. Data focusing on MpBC are limited. The aim of this study was to describe the clinicopathological features of MpBC and evaluate the prognosis of patients with MpBC.

Isatuximab in combination with cemiplimab in patients with relapsed/refractory multiple myeloma: A phase 1/2 study.

Background: Given the incurable nature of multiple myeloma (MM), efforts are made to improve the efficacy of anti-CD38 monoclonal antibodies via combinations with other potentially synergistic therapies. This Phase 1/2 trial (NCT03194867) was designed to determine whether cemiplimab (anti-PD-1) enhances the anti-myeloma activity of isatuximab (anti-CD38) in patients with relapsed and refractory multiple myeloma (RRMM), to confirm the feasibility of the combination, determine its efficacy, and further evaluate its safety.

Methods: Patients received isatuximab 10 mg/kg once weekly for 4 weeks followed by every 2 weeks (Isa), or isatuximab 10 mg/kg plus cemiplimab 250 mg every 2 (Isa + CemiQ2W) or every 4 weeks (Isa + CemiQ4W).

MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials.

Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized placebo-controlled phase 3 studies of 2-year ixazomib maintenance.

Multi-Gene Mutation Profiling by Targeted Next-Generation Sequencing in Premenopausal Breast Cancer.

Breast cancer has distinct etiology, prognoses, and clinical outcomes at premenopausal ages. Determination of the frequency of germline and somatic mutations will refine our understanding of the genetic contribution to premenopausal breast cancer susceptibility. We applied a comprehensive next generation sequencing-based approach to analyze blood and/or tissue samples of 54 premenopausal breast cancer patients treated in our clinic.

Cardiac mechanics in response to proteasome inhibition: a prospective study.

Aim: Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans.

Pomalidomide- and dexamethasone-based regimens in the treatment of refractory/relapsed multiple myeloma.

Pomalidomide is a potent immunomodulatory agent that is currently a standard of care backbone for the treatment of multiple myeloma (MM) patients in the relapsed/refractory setting after exposure to lenalidomide and a proteasome inhibitor. The present review addresses current knowledge regarding the clinical use of pomalidomide in relapsed myeloma patients. Pomalidomide has direct myeloma cell tumoricidal effects by activating proteasomal degradation of Ikaros and Aiolos transcription factors and also indirect effects by modulation of immune responses, interaction with bone marrow stromal cells, and inhibition of angiogenesis.

Comparison of MRI Features of Fat Fraction and ADC for Early Treatment Response Assessment in Participants with Multiple Myeloma.

Background An imaging-based predictor of response could provide prognostic information early during treatment course in patients with multiple myeloma (MM). Purpose To investigate if very early changes in bone marrow relative fat fraction (rFF) and apparent diffusion coefficient (ADC) histogram metrics, occurring after one cycle of induction therapy in participants with newly diagnosed MM, could help predict overall best response status. Materials and Methods This prospective study included participants with MM who were enrolled between August 2014 and December 2017.

Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review.

Introduction: The clinical outcome of HER2-positive breast cancer patients changed with the use of anti-Her therapies, though it still remains an aggressive and fatal disease. Implementation of immune checkpoint inhibitors in HER2-positive Breast cancer is a concept supported by the reported biological and preclinical data.

Methods: We conducted a systematic review of the current literature involving immune checkpoint inhibitors alone or in combination with targeted therapies or chemotherapy finalized or running in HER2-positive breast cancer.

Daratumumab plus CyBorD for patients with newly diagnosed light chain (AL) amyloidosis.

Primary systemic immunoglobulin light chain (AL) amyloidosis is caused by a plasma cell clone of, usually low, malignant potential that expresses CD38 molecules on their surface. Treatment of AL amyloidosis is based on the elimination of the plasma cell clone. The combination of cyclophosphamide-bortezomib-dexamethasone (CyBorD) is the most widely used and is considered a standard of care; however, complete hematologic response rates and organ response rates remain unsatisfactory.

Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study.

Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) ( = 14) or Kd ( = 11).

TP53 mutations determined by targeted NGS in breast cancer: a case-control study.

Background: Tumor protein 53 (TP53) gene mutations are identified in up to 37% of breast tumors especially in HER-2 positive and basal-like subtype. Previous studies have indicated TP53 mutations as a prognostic biomarker in breast cancer. However, most of these studies performed immunohistochemistry (IHC) for the detection of TP53 mutations.

Occupational Exposure and Multiple Myeloma Risk: An Updated Review of Meta-Analyses.

The precise etiology of multiple myeloma remains elusive, but both genetic and environmental factors have been suggested to contribute to disease risk. Several occupational categories and toxic agents have been implicated as potentially causative, yet findings from the literature are inconsistent. The aim of this review was to summarize and critically comment on the accumulated epidemiological evidence, across published meta-analyses, about the association between occupational exposure and risk of multiple myeloma.

Bone Marrow Microenvironment Interplay and Current Clinical Practice in Multiple Myeloma: A Review of the Balkan Myeloma Study Group.

The course of multiple myeloma (MM) is influenced by a variety of factors, including the specificity of the tumour microenvironment (TME). The aim of this review is to provide insight into the interplay of treatment modalities used in the current clinical practice and TME. Bortezomib-based triplets are the standard for MM first-line treatment.

Novel Nested-Seq Approach for SARS-CoV-2 Real-Time Epidemiology and In-Depth Mutational Profiling in Wastewater.

Considering the lack of effective treatments against COVID-19, wastewater-based epidemiology (WBE) is emerging as a cost-effective approach for real-time population-wide SARS-CoV-2 monitoring. Here, we report novel molecular assays for sensitive detection and mutational/variant analysis of SARS-CoV-2 in wastewater. Highly stable regions of SARS-CoV-2 RNA were identified by RNA stability analysis and targeted for the development of novel nested PCR assays.