Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial.

Introduction: In the OPTIMISMM trial, pomalidomide/bortezomib/dexamethasone (PVd) significantly prolonged median progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) in lenalidomide-exposed relapsed and refractory multiple myeloma (RRMM). We report final overall survival (OS) and updated efficacy analyses.

Methods: Adults with RRMM who had 1-3 prior regimens, including lenalidomide (≥ 2 cycles), were assigned (1:1) to PVd or Vd.

Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma.

Iberdomide is a next-generation cereblon (CRBN)-modulating agent in the clinical development in multiple myeloma (MM). The analysis of biomarker samples from relapsed/refractory patients enrolled in CC-220-MM-001 (ClinicalTrials.gov: NCT02773030), a phase 1/2 study, shows that iberdomide treatment induces significant target substrate degradation in tumors, including in immunomodulatory agent (IMiD)-refractory patients or those with low CRBN levels.

Immunomodulation of NK, NKT and B/T cell subtypes in relapsed/refractory multiple myeloma patients treated with pomalidomide along with velcade and dexamethasone and its association with improved progression-free survival.

Background: Multiple Myeloma (MM) patients exhibit dysregulated immune system, which is further weakened by chemotherapeutic agents. While cereblon-modulating agents, such as pomalidomide and lenalidomide, have been found to improve the immune profile, the efficacy of their impact in combination with other treatments is yet unknown.

Methods: We conducted an immune-profiling of a longitudinal cohort of 366 peripheral blood samples from the CC4047-MM-007 (OPTIMISMM, NCT01734928) study.

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma.

Background: Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.

Methods: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma.

Chronic Exposure to Chlorpyrifos Damages Thyroid Activity and Imbalances Hepatic Thyroid Hormones Signaling and Glucose Metabolism: Dependency of T3-FOXO1 Axis by Hyperglycemia.

Early life exposure to Endocrine Disruptor Chemicals (EDCs), such as the organophosphate pesticide Chlorpyrifos (CPF), affects the thyroid activity and dependent process, including the glucose metabolism. The damage of thyroid hormones (THs) as a mechanism of action of CPF is underestimated because the studies rarely consider that TH levels and signaling are customized peripherally. Here, we investigated the impairment of metabolism/signaling of THs and lipid/glucose metabolism in the livers of 6-month-old mice, developmentally and lifelong exposed to 0.

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial.

Background: Iberdomide is a novel cereblon E3 ligase modulator with enhanced tumouricidal and immune-stimulatory effects compared with immunomodulatory drugs. In preclinical myeloma models, iberdomide has shown synergy with dexamethasone, proteasome inhibitors, and CD38 monoclonal antibodies. We aimed to evaluate the safety and clinical activity of iberdomide plus dexamethasone in patients with heavily pretreated relapsed or refractory multiple myeloma.

Aiding early clinical drug development by elucidation of the relationship between tumor growth inhibition and survival in relapsed/refractory multiple myeloma patients.

Early prognosis of clinical efficacy is an urgent need for oncology drug development. Herein, we systemically examined the quantitative approach of tumor growth inhibition (TGI) and survival modeling in the space of relapsed and refractory multiple myeloma (MM), aiming to provide insights into clinical drug development. Longitudinal serum M-protein and progression-free survival (PFS) data from three phase III studies ( = 1367) across six treatment regimens and different patient populations were leveraged.

Model-based analysis for the population pharmacokinetics of iberdomide and its major active metabolite in healthy subjects and patients with relapsed and refractory multiple myeloma.

Aims: A parent-metabolite population pharmacokinetic (popPK) model of iberdomide and its pharmacologically active metabolite (M12) was developed and the influence of demographic and disease-related covariates on popPK parameters was assessed based on data from 3 clinical studies of iberdomide (dose range, 0.1-6 mg) in healthy subjects (n = 81) and patients with relapsed and refractory multiple myeloma (n 245).

Methods: Nonlinear mixed effects modelling was used to develop the popPK model based on data from 326 subjects across 3 clinical studies.

Pax8 and Nkx2-1 haploinsufficiencies differentially affect liver metabolic pathways.

Thyroid dysfunctions are associated with liver diseases ranging, in severity, from insulin resistance (IR) to hepatocellular carcinoma. The pathogenic mechanisms appear complex and are not attributable, exclusively, to the impaired thyroid hormone (TH) signalling. Using a mouse model of human congenital hypothyroidism, young double heterozygote for both NK2 homeobox 1 (Nkx2-1)- and Paired box 8 (Pax8)-null mutations (DHTP) mice, and single heterozygous Pax8+/- and Nkx2-1+/- mice, we studied the liver pathways, the endocrine and metabolic factors affected in conditions of different dysthyroidisms.

Ovarian Aging: Role of Pituitary-Ovarian Axis Hormones and ncRNAs in Regulating Ovarian Mitochondrial Activity.

The number of mitochondria in the oocyte along with their functions (e.g., energy production, scavenger activity) decline with age progression.

Pomalidomide, bortezomib, and dexamethasone at first relapse in lenalidomide-pretreated myeloma: A subanalysis of OPTIMISMM by clinical characteristics.

Objective: We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high-risk cytogenetic abnormalities in lenalidomide-pretreated patients with multiple myeloma at first relapse.

Methods: OPTIMISMM was a phase 3, multicenter, open-label, randomized study (NCT01734928; N = 559). The primary endpoint was progression-free survival (PFS).

Sample-Pooling Strategy for SARS-CoV-2 Detection among Students and Staff of the University of Sannio.

Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, it has been clear that testing large groups of the population was the key to stem infection and prevent the effects of the coronavirus disease of 2019, mostly among sensitive patients. On the other hand, time and cost-sustainability of virus detection by molecular analysis such as reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) may be a major issue if testing is extended to large communities, mainly asymptomatic large communities. In this context, sample-pooling and test grouping could offer an effective solution.

Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse.

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated superior efficacy vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide, including those refractory to lenalidomide. This analysis evaluated outcomes in patients at first relapse (N = 226) by lenalidomide-refractory status, prior bortezomib exposure, and prior stem cell transplant (SCT). Second-line PVd significantly improved PFS vs Vd in lenalidomide-refractory (17.

Pomalidomide-bortezomib-dexamethasone in relapsed or refractory multiple myeloma: Japanese subset analysis of OPTIMISMM.

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib and dexamethasone (PVd) significantly improved the progression-free survival (PFS) and the overall response rate (ORR) vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma. All patients were previously treated with lenalidomide (70% refractory to lenalidomide) and had received one to three prior regimens. Here we report the first efficacy and safety analysis of PVd vs Vd in Japanese patients with relapsed or refractory multiple myeloma.

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial.

Background: As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.

Cereblon gene expression and correlation with clinical outcomes in patients with relapsed/refractory multiple myeloma treated with pomalidomide: an analysis of STRATUS.

We analyzed gene expression levels of CRBN, cMYC, IRF4, BLIMP1, and XBP1 in 224 patients with multiple myeloma treated with pomalidomide and low-dose dexamethasone in the STRATUS study (ClinicalTrials.gov: NCT01712789; EudraCT number: 2012-001888-78). Clinical responses were observed at all CRBN expression levels.

Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma.

Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible.