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A systematic review and meta-analysis of carfilzomib-associated thrombocytopenia as an adverse event in patients with multiple myeloma.

BackgroundCarfilzomib is a second-generation proteasome inhibitor (PI) used for combination therapy with dexamethasone and/or lenalidomide in patients with relapsed or refractory multiple myeloma. Reports indicate that PIs have a unique toxicity profile that includes thrombocytopenia as a hematologic adverse event; however, its occurrence has not yet been quantified systematically.ObjectivesThe main objective of our systematic review and meta-analysis is to investigate the incidence of thrombocytopenia in patients with multiple myeloma after treatment with carfilzomib.DesignSelection of studie

Contemporary Challenges in Venous Thromboembolism: Evolving Populations and Implications for Management and Risk Stratification.

Venous thromboembolism (VTE) remains a major cause of morbidity and mortality globally. The incidence of VTE continues to increase over time, contributed to by demographic shifts and emerging risk factors, such as novel cancer treatments and exposure to gender-affirming hormonal therapies. While the introduction of direct oral anticoagulants (DOACs) revolutionized VTE management, increasing complexity in select patient cohorts has driven the need for alternative treatment strategies, including pharmacological and interventional approaches. Concurrently, contemporary patient populations have ex

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… Emerging factor XI inhibitors may help reduce bleeding, although more evidence is required. Box 1 summarises some of the key treatment considerations. Treatment key messages. … Targeting factor XI and factor XIa to prevent thrombosis Blood 2024 143 1465 1475 10.1182/blood.2023020722 38142404 PMC11033593 84. …

Chinese Herbal Medicine Is Helpful for Survival Improvement in Patients With Multiple Myeloma in Taiwan: A Nationwide Retrospective Matched-Cohort Study.

Aim of the studyThe purpose of this study is to demonstrate that Chinese herbal medicine is beneficial for survival improvement in patients with multiple myeloma.Materials and methodsWe performed a 1:1 propensity score-matched cohort study to analyze patients with multiple myeloma diagnosed between January 1, 2002, and December 31, 2012, through the Taiwanese National Health Insurance Research Database. Patients who received Chinese herbal medicine therapy from the initial date of diagnosis of multiple myeloma to December 31, 2012, were included in the Chinese herbal medicine group. Patients w

Evidence-based Korean guidelines for the clinical management of multiple myeloma: addressing 12 key clinical questions.

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM. In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treatment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These r

Lenalidomide versus bortezomib maintenance after frontline autologous stem cell transplantation for multiple myeloma.

Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1-21 of 28 day cycles) followed by 10-15 mg/day for 2 years. The

Risk and response adapted therapy following autologous stem cell transplant in patients with newly diagnosed multiple myeloma (RADAR (UK-MRA Myeloma XV Trial): study protocol for a phase II/III randomised controlled trial.

IntroductionMultiple myeloma is a plasma cell malignancy that accounts for 1%-2% of newly diagnosed cancers.At diagnosis, approximately 20% of patients can be identified, using cytogenetics, to have inferior survival (high-risk). Additionally, standard-risk patients, with detectable disease (minimal residual disease (MRD)-positive) postautologus stem cell transplant (ASCT), fare worse compared with those who do not (MRD-negative). Research is required to determine whether a risk-adapted approach post-ASCT could further improve patient outcomes.MethodsRADAR is a UK, multicentre, risk-adapted, r

Perspectives on the Risk-Stratified Treatment of Multiple Myeloma.

The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article d

Lenalidomide as maintenance treatment for patients with multiple myeloma after autologous stem cell transplantation: A pharmaco-economic assessment.

OBJECTIVE: Autologous stem cell transplantation (ASCT) has improved progression-free survival (PFS) and overall survival in eligible patients with newly diagnosed multiple myeloma (NDMM); however, relapse occurs. Maintenance therapy with lenalidomide (Len-Mt) extends survival and delays relapse and the subsequent initiation of costly second-line regimens. Here, we report the cost-effectiveness of Len-Mt following ASCT from a Dutch healthcare service perspective. METHODS: A partitioned survival model was developed to assess the lifetime costs and benefits for patients with NDMM. Efficacy was t

Targeting Proteasomes in Cancer and Infectious Disease: A Parallel Strategy to Treat Malignancies and Microbes.

Essential core pathways of cellular biology are preserved throughout evolution, highlighting the importance of these pathways for both bacteria and human cancer cells alike. Cell viability requires a proper balance between protein synthesis and degradation in order to maintain integrity of the proteome. Proteasomes are highly intricate, tightly regulated multisubunit complexes that are critical to achieve protein homeostasis (proteostasis) through the selective degradation of misfolded, redundant and damaged proteins. Proteasomes function as the catalytic core of the ubiquitin-proteasome pathw

The clinical management of lenalidomide-based therapy in patients with newly diagnosed multiple myeloma.

Lenalidomide is an integral, yet evolving, part of current treatment pathways for both transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). It is approved in combination with dexamethasone as first-line therapy for transplant-ineligible patients with NDMM, and as maintenance treatment following autologous stem cell transplantation (ASCT). Although strong clinical trial evidence has supported the integration of lenalidomide into current treatment paradigms for NDMM, applying those paradigms to individual patients and determining which patients are

Общенациональная реализация проекта по обслуживанию линалидомида в множестве миеломы: ретроспективное исследование реального мира.

Технология леналидомида (LM) показала, что в клинических испытаниях выживает без прогрессирования (PFS) и в целом выживает (OS). ЛМ - это рекомендуемый стандарт лечения у пациентов с недавно диагностированным множественным миэломой (ММ) после гипердозы мелфалана и аутологической трансплантации стволовых клеток (HDM-ASCT). В Дании с июня для всех пациентов, проходящих курс лечения с помощью HDM-ASCT, был утвержден и финансируется из государственного бюджета. 2019. Пациенты с недавно поставленным диагнозом MM лечатся своим первым HDM-ASCT в июне 2019 и март 2022 были включены и использованы до к

Управление пациентами с недавно поставленным диагнозом множественной миеломы, имеющими право на аутологическую трансплантацию стволовых клеток: заявление о позиции Медицинской и научной консультативной группы Австралии по миеломе.

Выживание вновь диагностированных пациентов с множественной миеломой значительно улучшилось в прошлом. 20 годы со значительными терапевтическими достижениями. Несмотря на это, высокодозированная химиотерапия, за которой следует аутологическая трансплантация стволовых клеток, по-прежнему является стандартом ухода за вновь поставленными диагнозами пациентами, которые считаются имеющими право на трансплантацию. Здесь мы резюмируем рекомендации Медицинской и научной консультативной группы Австралии для пациентов, считающихся подходящими для высокодозированной химиотерапии и аутологической транспла

Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma.

The evolving paradigm of continuous therapy and maintenance treatment approaches in multiple myeloma (MM) offers prolonged disease control and improved outcomes compared to traditional fixed-duration approaches. Potential benefits of long-term strategies include sustained control of disease symptoms, as well as continued cytoreduction and clonal control, leading to unmeasurable residual disease and the possibility of transforming MM into a chronic or functionally curable condition. "Continuous therapy" commonly refers to administering a doublet or triplet regimen until disease progression, whe

How First-Line Therapy is Changing in Transplant-Eligible Multiple Myeloma Patients.

Multiple myeloma is a malignant haematological neoplasm characterised by the proliferation of plasma cells in the bone marrow. Each year, over 35,000 new cases are diagnosed in the United States, and nearly 13,000 patients die from the disease.1 The main cause of morbidity is bone disease, characterised by osteolytic lesions, which, unlike other malignancies that metastasise to bone, are not followed by new bone formation.2 Other major clinical manifestations include anaemia, hypercalcemia, renal failure, and an increased risk of infections. Approximately 1-2% of patients present with extramed

Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions.

Purpose of reviewMultiple myeloma (MM) is a biologically heterogeneous malignancy with relatively uniform treatment paradigms. This review aims to assess the growing role of Minimal Residual Disease (MRD) assessment in facilitating response-adapted therapeutic decision making to individualize therapy in MM.Recent findingsMRD has been repeatedly demonstrated to provide strong prognostic information, superseding traditional IMWG response criteria. The use of MRD to modulate therapy remains controversial. Here, we review the existing landscape of MRD-adapted trial designs in both induction/consol

Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an ad hoc expert panel.

The introduction of new therapeutic agents for multiple myeloma (MM), including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has improved the outcomes of patients but, in parallel, has changed the frequency and epidemiology of thrombotic events. Thrombosis is now a significant cause of morbidity and mortality in MM patients, and optimal thromboprophylaxis is far from being reached. Moving from the recognition that the above issue represents an unmet clinical need, an expert panel assessed the scientific literature and composed a framework of recommendations for imp

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfi

Prediction of Solitary Plasmacytoma of Bone in Elderly Patients: A Nomogram and a Risk Classification System for Overall Survival.

BACKGROUND: Solitary plasmacytoma of bone (SPB) is an isolated plasmacytoma of bone origin, most commonly seen in the elderly, with a poor prognosis. So far, there is no precise nomogram to predict the overall survival (OS) of elderly patients with SPB. Our goal is to construct and validate a nomogram for elderly patients with SPB. METHODS: This study collected all elderly patients with SPB in the Surveillance, Epidemiology and End Results (SEER) database from 2000 to 2018, and the variables included were age, sex, race, marital status, primary site, grade, stage, surgery, chemotherapy, and r

Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.

Alternative splicing (AS) is the central mechanism of transcriptional regulation and generates diverse splice variants that influence protein structure, function, and intracellular activity. AS plays critical roles in tissue differentiation, organ development, and disease progression. This review focuses on the pivotal roles of AS in bone biology, highlighting its regulatory effects on osteoblasts, osteoclasts, chondrocytes, bone matrix remodeling, and bone remodeling, as well as the involvement of AS-related RNA-binding proteins in these processes. We also emphasize bone-specific AS events an

Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (ra