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2.
Eur J Haematol ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654611

RESUMEN

OBJECTIVES: To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM). METHODS: INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA-IXA, and REMIX. RESULTS: Overall, 391/100/68 were lenalidomide-naïve/-exposed/-refractory and 37/411/110 were PI-naïve/-exposed/-refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression-free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide-naïve/exposed/refractory patients. Median DOT and PFS in PI-naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable. CONCLUSION: IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide- and/or PI-nonrefractory versus refractory patients.

3.
Haematologica ; 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38426294

RESUMEN

TOURMALINE-MM1, the only blinded randomized study in patients with relapsed and/or refractory multiple myeloma (RRMM; ≥1 prior therapy) in the last 10 years, investigated ixazomib+lenalidomide+dexamethasone (IRd) versus lenalidomide+dexamethasone (Rd). Final overall survival (OS) data were based on a median follow-up of 85 months. In RRMM trials where patients have had 1-3 relapses after initial treatment, a high proportion receive subsequent therapy. Application of salvage therapies in blinded trials and newer modes of therapy can increasingly complicate the interpretation of OS. This analysis explores the impact of subsequent therapies on OS outcomes in TOURMALINE-MM1. The inverse probability of censoring weights (IPCW) method, marginal structural model (MSM), and rank preserving structural failure time model (RPSFTM) were utilized to adjust for confounding on OS, introduced by subsequent therapies. Analyses were conducted for the intentto-treat (ITT) population and ≥2 prior lines subgroup. Unadjusted hazard ratio (HR) for IRd versus Rd was 0.94 (95% confidence interval [CI]: 0.78-1.13) in the ITT population. After adjusting for the impact of subsequent therapies by the RPSFTM method, estimated HR for IRd versus Rd in the ITT population was 0.89 (95% CI: 0.74-1.07). Adjusting with IPCW and MSM methods also showed an improvement in HR, favoring IRd. IRd may be particularly beneficial in patients with ≥2 prior lines of therapy (IPCW and MSM HR=0.52, 95% CI: 0.30-0.88; RPSFTM HR=0.68, 95% CI: 0.51-0.91). These analyses highlight the growing challenge of demonstrating OS benefit in multiple myeloma patients and the importance of assessing confounding introduced by subsequent therapies when interpreting OS.

4.
Environ Pollut ; 346: 123598, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38369088

RESUMEN

Microplastics (MPs) contamination has been reported in all environmental compartments, but very limited information is available at higher-altitude lakes. Nainital Lake, located at a high altitude in the Indian Himalayas, has various ecosystem services and is the major source of water for Nainital town, but the MP abundance is still unknown. This study presents the first evidence of the abundance and distribution of MP in Nainital Lake. Surface water and sediment samples were analysed from 16 different sites in and around the catchment area of Nainital Lake. The MP were observed in all the samples, and their abundance in surface water was 8.6-56.0 particles L-1 in the lake and 2.4-88.0 particles L-1 in hotspot sites. In the surface sediment, MP abundance ranged from 0.4-10.6 particles g-1, while in the hotspot sediment, the mean abundance was 0.6 ± 0.5 particles g-1. Fibers were the dominant MP, while 0.02-1 mm were the predominant size of MP particles. The results of chemical characterization showed the presence of six polymers, among which high-density polyethylene was the most abundant. The Polymer Hazard Index assessment classified the identified polymers as low-to high-risk categories, with a higher abundance of low- (polypropylene) and medium- (polyethylene)-risk polymers. Tourist activities and run-off catchments can be considered the major sources of MP, which can affect the ecosystem. Minimal concentrations of MP were observed in the tube well and drinking water, which depicts the direct risks to humans and, thus, the need for remedial measures to prevent MP contamination in drinking water. This study improves the knowledge of MP contamination in the higher-altitude freshwater lake, which can be the major pathway for the transport of MP to the rivers, and also emphasizes the need for waste management in Nainital town.


Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Humanos , Microplásticos/análisis , Plásticos/análisis , Lagos/química , Ecosistema , Agua Potable/análisis , Altitud , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Polietileno/análisis , India
5.
Br J Haematol ; 204(4): 1193-1206, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38393718

RESUMEN

Multiple myeloma is a bone marrow-based plasma cell tumour that develops from asymptomatic pre-cursor conditions smouldering myeloma and monoclonal gammopathy of uncertain significance and all are characterised by the presence of a monoclonal protein in the blood. Diagnosis and distinction between these conditions is based on blood tests, the bone marrow biopsy and cross sectional imaging. There are various risk stratification models that group patients with smouldering myeloma into risk groups based on risk of progression to symptomatic disease. Management is mainly observational for patients with smouldering myeloma although clinical trials for high-risk disease may be available. Restaging is required if evidence for progression.


Asunto(s)
Hematología , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Mieloma Múltiple Quiescente , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Mieloma Múltiple/patología , Células Plasmáticas/patología , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/terapia , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple Quiescente/diagnóstico , Mieloma Múltiple Quiescente/terapia , Mieloma Múltiple Quiescente/patología , Progresión de la Enfermedad
6.
Future Oncol ; 20(14): 935-950, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38197267

RESUMEN

Aim: We pooled data from three observational studies (INSIGHT MM, UVEA-IXA and REMIX) to investigate the real-world effectiveness of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory myeloma. Materials & methods: INSIGHT MM was a prospective study conducted in countries across Europe, Asia and North/Latin America while UVEA-IXA and REMIX were multicenter, retrospective/prospective studies conducted in Europe. Patients who had received IRd as ≥2nd line of therapy were analyzed. Primary outcomes were time-to-next treatment (TTNT) and progression-free survival (PFS). Results: Overall, 564 patients were included (median follow-up: 18.5 months). Median TTNT and PFS were 18.4 and 19.9 months; both outcomes were numerically longer for earlier versus later lines. Median treatment duration was 14.0 months. Overall response rate was 64.6%. No new safety concerns were noted. Conclusion: The effectiveness of IRd in routine practice appears similar to the efficacy observed in TOURMALINE-MM1. IRd benefit in earlier versus later lines was consistent with previous reports.


Asunto(s)
Glicina , Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos de Boro/uso terapéutico , Dexametasona/uso terapéutico , Glicina/análogos & derivados , Lenalidomida/uso terapéutico , Estudios Multicéntricos como Asunto , Mieloma Múltiple/tratamiento farmacológico , Estudios Prospectivos , Estudios Retrospectivos
8.
Clin Lymphoma Myeloma Leuk ; 24(2): e40-e49.e3, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37996265

RESUMEN

BACKGROUND: In multiple myeloma (MM), improving our understanding of routine clinical practice and the effectiveness of agents outside of clinical trials is important. TOURMALINE-MM1 data resulted in approval of ixazomib for MM patients who have received ≥ 1 prior therapy. PATIENTS AND METHODS: UVEA-IXA comprised a retrospective chart review in the early access program, and a prospective 1-year follow-up period. Eligible patients had had a biochemical and/or symptomatic relapse after 1-3 prior lines of therapy; no anti-MM therapy for > 3 cycles at the start of ixazomib therapy; and an Eastern Cooperative Oncology Group performance score of 0-2. Lenalidomide- or proteasome inhibitor (PI)-refractory patients were ineligible. Primary endpoints were response and progression-free survival (PFS). RESULTS: Of 357 enrolled patients, 309 were evaluable; most patients received ixazomib alongside lenalidomide (98%) and dexamethasone (97%); 61% had received 2-3 prior lines of therapy. Median PFS was 15.6 months (95% confidence interval [CI]: 12.0-20.6) in all evaluable patients, and 19.6 (95% CI: 12.1-27.0) and 13.9 (95% CI: 10.1-18.1) months in patients who received 1 and ≥ 2 prior lines of therapy, respectively. The overall response rate was 67% in all evaluable patients, and 72% and 63%, respectively, in patients who received 1 and ≥ 2 prior lines of therapy. Median overall survival was 35.5 months. The ixazomib safety profile was consistent with previous reports. CONCLUSION: This study supports ixazomib-based therapy as an effective and tolerable treatment in the real-world. Outcomes were favorable in patients with 1 or ≥ 2 prior lines of therapy who were not lenalidomide- or PI-refractory.


Asunto(s)
Compuestos de Boro , Glicina/análogos & derivados , Mieloma Múltiple , Humanos , Lenalidomida/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Dexametasona/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Úvea
9.
Eur J Haematol ; 112(4): 547-553, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38116695

RESUMEN

OBJECTIVE: To describe determinants of persisting humoral and cellular immune response to the second COVID-19 vaccination among patients with myeloma. METHODS: This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID-19 vaccination dates. Myeloma patients had an Anti-S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. RESULTS: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti-S antibody levels (<50 IU/mL) doubled during this interval (p = .023) and, in the 47 participants with T-spot data, there was a 25% increase negative T-spot tests (p = .008). Low anti-S antibody levels prior to the third vaccination were predicted by lower Anti-S antibody level and negative T-spot status after the second vaccine. Independent determinants of a negative T-spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti-S antibody levels. CONCLUSIONS: Negative T-spot results predict low Anti-S antibody levels (<50 IU/mL) following a second COVID-19 vaccination and a number of biomarkers predict T cell responses in myeloma patients.


Asunto(s)
COVID-19 , Mieloma Múltiple , Humanos , Linfocitos T , COVID-19/prevención & control , Vacunas contra la COVID-19 , Mieloma Múltiple/terapia , Anticuerpos , Vacunación , Anticuerpos Antivirales , Inmunidad Celular
10.
Eur J Haematol ; 112(5): 701-713, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38146208

RESUMEN

OBJECTIVES: To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe. METHODS: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. RESULTS: Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). CONCLUSIONS: From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.


Asunto(s)
Mieloma Múltiple , Talidomida/análogos & derivados , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/epidemiología , Lenalidomida/uso terapéutico , Estudios Retrospectivos , España , Dexametasona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
11.
Front Oncol ; 13: 1282569, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38098501

RESUMEN

Introduction: Late presentation of multiple myeloma (MM) heightens the risk of complication risks, including end-organ damage. This study aimed to: 1) detail the diagnostic journey of MM patients, encompassing symptoms, initial diagnoses, and healthcare professionals met; 2) establish the median duration from symptom onset to MM diagnosis; and 3) examine factors linked to timely MM diagnosis within 12 weeks. Methods: A total of 300 adults self-reporting MM were analysed from the Rare and Undiagnosed Diseases cohort Study (RUDY). The RUDY study is a web-based platform, where participants provide dynamic consent and self-report their MM diagnosis and information about their diagnostic journey. This includes the estimated date of initial potential first symptoms, descriptions of these symptoms, the healthcare professionals they consulted, and other diagnoses received before the MM diagnosis. Descriptive statistics, combinatorial analyses and logistic regression analyses were used to describe and examine the diagnostic journey of individuals with MM. Results: Overall, 52% of the participants reported other diagnoses before MM diagnosis, with musculoskeletal disorders (47.8%), such as osteoporosis, costochondritis, or muscle strains, being the most common. The most prevalent initial reported symptom was back pain/vertebral fractures (47%), followed by chest/shoulder pain, including rib pain and fractures (20%), and fatigue/tiredness (19.7%). 40% of participants were diagnosed by direct referral from primary care to haematology without seeing other healthcare professionals whilst 60% consulted additional specialists before diagnosis. The median time from symptom onset to MM diagnosis was 4 months (IQR 2-10 months, range 0-172). Seeing an Allied Healthcare Professional such as a physiotherapist, chiropractor or an osteopath (OR = 0.25, 95% CI [0.12, 0.47], p <0.001), experiencing infection symptoms (OR = 0.32, 95% CI [0.13, 0.76], p = 0.013), and having chest or shoulder pain (OR = 0.45, 95% CI [0.23, 0.86], p = 0.020) were associated with a lower likelihood of being diagnosed with MM within 12 weeks. Older age (OR = 1.04, 95% CI [1.02, 1.07], p = 0.001) was associated with a higher likelihood of diagnosis within 12 weeks. Discussion: Developing resources for allied health professionals may improve early recognition of MM.

12.
Platelets ; 34(1): 2264940, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37822056

RESUMEN

Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.


What is the context?Multiple myeloma is associated with increased risk of thrombosis, although the potential role of platelets in this has not been evaluated.What is new?We show in this pilot study that multiple myeloma and its precursor states of smoldering myeloma and monoclonal gammopathy of undetermined significance are associated with increased levels of platelet responses. This is further exacerbated by treatment with the immunomodulatory drug lenalidomide.What is the impact?This study suggests that more detailed studies are warranted to explore the mechanisms that cause these effects in a larger population of patients, since this may reveal new approaches to prevent myeloma-associated thrombotic complications.


Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Trombosis , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Lenalidomida/farmacología , Lenalidomida/uso terapéutico , Proyectos Piloto , Trombosis/complicaciones , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones
13.
Hemasphere ; 7(9): e942, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37663672

RESUMEN

We used a modified Delphi approach to establish areas of consensus and nonconsensus regarding the utility of determining measurable residual disease (MRD) to assess multiple myeloma (MM) treatment response, which may inform disease management and design of future clinical trials. This modified Delphi study incorporated 2 iterative rounds of surveys to evaluate the opinions of an expert panel of 61 practicing hematological oncologists from across 14 countries in Europe concerning the use of MRD testing in MM management. Survey 1 assessed experts' opinions on MRD testing in different clinical situations and associated challenges. Survey 2 focused on the lack of consensus areas identified in survey 1. Consensus to an individual question was defined a priori as 75% agreement or disagreement by the panel. From the 2 rounds of surveys, the experts reached consensus agreement that MRD testing should be performed in newly diagnosed or relapsed patients who achieved complete response (CR) or better after transplantation. In transplant-ineligible patients, experts recommended MRD testing in those who are ≤70 years old and in CR. If a patient was previously positive on positron-emission tomography and computed tomography (PET/CT), both MRD and PET/CT should be assessed at CR. MRD testing should be performed ≤6 months after transplantation and every 6-12 months in continuously treated patients in CR. There was no consensus on making treatment decisions based on MRD status. MRD testing is an important component of clinical management in MM. Additional data will further clarify the role of MRD in guiding treatment decisions.

14.
Blood Cancer J ; 13(1): 116, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37528088

RESUMEN

Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies (mAbs), guidance on infection monitoring, prophylaxis and treatment is required. This review provides consensus recommendations from a panel of 13 global experts, following a meeting in August 2022. The meeting objective was to review existing literature and identify relevant information on infections with all BsAbs in patients with MM, as well as to discuss clinical experience of experts in managing these infections. The recommendations outlined here can be used to guide management of infection risk factors, such as hypogammaglobulinemia and neutropenia. In addition, they can be used to guide the monitoring, prophylaxis, and treatment of bacterial, viral and fungal infections, including emerging infections of interest, such as coronavirus 2019 (COVID-19), and the use of vaccinations prior to and during BsAb treatment. The recommendations have been graded by the panel based on level of data available. Key recommendations include universal herpes simplex and varicella zoster virus prophylaxis, screening for hepatitis B virus reactivation risk in all patients, monthly intravenous immunoglobulin treatment for immunoparesis and in the absence of life-threatening infectious manifestations, use of colony-stimulating factors in patients with Grade 3 neutropenia, universal pneumocystis jirovecii pneumonia prophylaxis and no routine anti-fungal prophylaxis.


Asunto(s)
Agammaglobulinemia , Anticuerpos Biespecíficos , COVID-19 , Mieloma Múltiple , Neutropenia , Humanos , Mieloma Múltiple/complicaciones , Anticuerpos Biespecíficos/efectos adversos , Consenso , Agammaglobulinemia/complicaciones , COVID-19/complicaciones
15.
Aesthet Surg J Open Forum ; 5: ojad073, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37638341

RESUMEN

Background: Gynecomastia surgery is one of the most common aesthetic procedures in males. There is a lack of objective analytical parameters to judge outcomes. In this study, the authors aim to introduce novel anthropometric measurements and analysis techniques for the objective assessment of surgical outcomes based on specific aesthetic targets. Objectives: To introduce quantification of gynecomastia surgery outcomes and compare the results among the different grades of gynecomastia. Methods: A total of 192 patients with gynecomastia were included. The patient cases were grouped according to grades and a set of anthropometric measurements were taken both before the operation and 6 months postoperatively. Liposuction and glandular excision were done through minimal incisions in all grades of gynecomastia, with the addition of ultrasound and nipple areola complex (NAC) lifting plaster in selected Grade 3 and all Grade 4 cases. Results: A statistically significant improvement in the perimeter of the triangular relationship of sternal notch and nipples, the elevation of the NAC, the reduction of the area of the NAC, and the correction of asymmetry of the chest were seen in all grades of gynecomastia, with increased differences in higher grades. Conclusions: A systematic objective analysis of the specific aesthetic targets helps to reliably compare results in a standard way and for carrying out improvisation of surgeons' techniques. Meanwhile, this approach helps identifying the need for customization, eventually providing symmetric and aesthetically pleasing surgical results.

16.
N Engl J Med ; 389(11): 1009-1022, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37646702

RESUMEN

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. The primary objectives of phase 1 (dose-escalation cohort) were to assess safety and pharmacokinetics and to identify the dose and schedule for phase 2. In phase 2 (dose-expansion cohort), objectives included the assessment of the overall response (partial response or better), safety, and efficacy of mezigdomide plus dexamethasone at the dose and schedule determined in phase 1. RESULTS: In phase 1, a total of 77 patients were enrolled in the study. The most common dose-limiting toxic effects were neutropenia and febrile neutropenia. On the basis of the phase 1 findings, investigators determined the recommended phase 2 dose of mezigdomide to be 1.0 mg, given once daily in combination with dexamethasone for 21 days, followed by 7 days off, in each 28-day cycle. In phase 2, a total of 101 patients received the dose identified in phase 1 in the same schedule. All patients in the dose-expansion cohort had triple-class-refractory multiple myeloma, 30 patients (30%) had received previous anti-B-cell maturation antigen (anti-BCMA) therapy, and 40 (40%) had plasmacytomas. The most common adverse events, almost all of which proved to be reversible, included neutropenia (in 77% of the patients) and infection (in 65%; grade 3, 29%; grade 4, 6%). No unexpected toxic effects were encountered. An overall response occurred in 41% of the patients (95% confidence interval [CI], 31 to 51), the median duration of response was 7.6 months (95% CI, 5.4 to 9.5; data not mature), and the median progression-free survival was 4.4 months (95% CI, 3.0 to 5.5), with a median follow-up of 7.5 months (range, 0.5 to 21.9). CONCLUSIONS: The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects. (Funded by Celgene, a Bristol-Myers Squibb Company; CC-92480-MM-001 ClinicalTrials.gov number, NCT03374085; EudraCT number, 2017-001236-19.).


Asunto(s)
Antineoplásicos , Dexametasona , Mieloma Múltiple , Ubiquitina-Proteína Ligasas , Humanos , Anticuerpos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Lenalidomida/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Neutropenia/inducido químicamente , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Administración Oral , Recurrencia
18.
Nanoscale Adv ; 5(10): 2724-2742, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37205287

RESUMEN

Transition-metal chalcogenide nanostructures provide a unique material platform to engineer next-generation energy storage devices such as lithium-ion, sodium-ion, and potassium-ion batteries and flexible supercapacitors. The transition-metal chalcogenide nanocrystals and thin films have enhanced electroactive sites for redox reactions and hierarchical flexibility of structure and electronic properties in the multinary compositions. They also consist of more earth-abundant elements. These properties make them attractive and more viable new electrode materials for energy storage devices compared to the traditional materials. This review highlights the recent advances in chalcogenide-based electrodes for batteries and flexible supercapacitors. The viability and structure-property relation of these materials are explored. The use of various chalcogenide nanocrystals supported on carbonaceous substrates, two-dimensional transition metal chalcogenides, and novel MXene-based chalcogenide heterostructures as electrode materials to improve the electrochemical performance of lithium-ion batteries is discussed. The sodium-ion and potassium-ion batteries offer a more viable alternative to lithium-ion technology as they consist of readily available source materials. Application of various transition metal chalcogenides such as MoS2, MoSe2, VS2, and SnSx, composite materials, and heterojunction bimetallic nanosheets composed of multi-metals as electrodes to enhance the long-term cycling stability, rate capability, and structural strength to counteract the large volume expansion during the ion intercalation/deintercalation processes is highlighted. The promising performances of layered chalcogenides and various chalcogenide nanowire compositions as electrodes for flexible supercapacitors are also discussed in detail. The review also details the progress made in new chalcogenide nanostructures and layered mesostructures for energy storage applications.

19.
Aesthet Surg J Open Forum ; 5: ojac095, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36866186

RESUMEN

Background: Gynecomastia is defined as a benign enlargement of male breast glandular tissue. It is the most common breast condition in male, and the prevalence ranges from 32% to 72%. No standardized treatment exists for gynecomastia. Objectives: The authors treat gynecomastia patient with liposuction and complete gland excision through periareolar incision without skin excision. In case of skin redundancy, the authors use their special technique called nipple areola complex (NAC) plaster lift technique. Methods: The authors conducted the retrospective analysis of patient who underwent gynecomastia surgery between January 2020 and December 2021 at Chennai Plastic Surgery. All patients were treated with liposuction, gland excision, and NAC lifting plaster when required. The follow-up period ranges from 6 to 14 months. Results: A total of 448 patients (896 breasts) were included in our study with average age of 26.6 years. Grade II gynecomastia was most common in our study. The average BMI of the patients was 27.31 kg/m2. One hundred and sixteen patients (25.9%) experienced some form of complication. Seroma was most common complications in our study followed by superficial skin necrosis. Patient satisfaction rate was high in our study. Conclusions: Gynecomastia surgery is safe and highly rewarding procedure for surgeons. Various technologies and methods like liposuction, complete gland excision, and NAC lifting plaster technique should be adopted in gynecomastia treatment to give a better patient satisfaction. Complications are common in gynecomastia surgery but easily manageable.

20.
Blood ; 141(6): 557-558, 2023 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-36757729
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