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CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival.

Surface antigens are commonly used in flow cytometry assays for the diagnosis of multiple myeloma (MM). Some of these are directly involved in MM pathogenesis or interactions with the microenvironment, but most are used for either diagnostic or prognostic purposes. In a previous study, we showed that in-vitro, CD24-positive plasma cells exhibit a less tumorigenic phenotype. Here, we assessed the prognostic importance of CD24 expression in patients newly diagnosed with MM as it correlates to their clinical course. Immunophenotyping by flow cytometry of 124 patients uniformly treated by a bortez

Meaningful change in patient-reported outcomes after CAR-T for multiple myeloma: differences by race and ethnicity.

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Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with

Outcome of therapy-related myeloid neoplasms treated with azacitidine.

BackgroundTherapy-related myeloid neoplasms (t-MN), including myelodysplastic syndromes and acute myeloid leukemia (t-MDS and t-AML) are associated to clinical and biologic unfavorable prognostic features, including high levels of DNA methylation.MethodsWe retrospectively evaluated 50 t-MN patients (34 MDS and 16 AML) selected among all patients receiving azacitidine (AZA) at 10 Italian Hematology Centers. Patients had developed a t-MN at a median of 6.5 years (range 1.7- 29) after treatment of the primary tumor (hematological neoplasm, 27 patients; solid tumor, 23 patients).ResultsThe overall

Profile of pomalidomide and its potential in the treatment of myelofibrosis.

Myelofibrosis, a Philadelphia-negative myeloproliferative neoplasm, is in a new treatment era after the discovery of the JAK2V617F mutation in 2005. JAK inhibitors boast improvements in disease-related symptoms, splenomegaly, and overall survival; however, treatment of myelofibrosis remains a challenge, given the lack of improvement in cytopenias with these agents. Second-generation immunomodulatory agents, such as pomalidomide, have shown efficacy in myelofibrosis-associated anemia within multiple clinical trials. Five major pomalido-mide clinical trials have been completed to date, and demon

Воздействие возраста на выживание и чрезмерную смертность после аналоговой трансплантации клеток у недавно диагностированных пациентов с миеломой.

Несмотря на наличие новых агентов, автологическая трансплантация гематопоиетических клеток (auto-HCT) по-прежнему является стандартом лечения вновь диагностированных пациентов с множественными миеломами (MM). На основе информации о воздействии возраста на общее выживание (СЗ), отсутствие прогресса в выживании (ПФС), частотность рецидивов, невозобновляемая смертность (НМС) и чрезмерная смертность (с учетом общей смертности населения) были исследованы 61,797 Пациенты MM пересажены между 2013 и 2017. Средний возраст в автоHCT был 60.8 (дальность, 18.1-83.2) лет, из которых 2.0% были 18-39 годы, 6

Infection events in patients with newly diagnosed multiple myeloma with anti-CD38 monoclonal antibody-based first line regimens: A multicentric Italian experience.

Multiple myeloma (MM) is a malignancy characterized by the clonal proliferation of plasma cells. It accounts for approximately 1% of all cancers and is the second most common hematologic malignancy after lymphoma. Infections represent a major cause of morbidity and mortality in patients with newly diagnosed multiple myeloma (NDMM), contributing to approximately 45% of early deaths, particularly in elderly individuals and during the initial months of therapy. Current treatment options for MM, including anti-CD38 monoclonal antibodies (CD38 mAbs), proteasome inhibitors, immunomodulatory drugs (s

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… Cytogenetic analysis at diagnosis was available in 19 of 20 patients (95%), and high-risk cytogenetics were identified in 7 of 19 patients (37%). The Immunoglobulin (Ig) dosage at diagnosis was: IgG 488 (range 331-1.019), IgA 114 (range 30-1705) and IgM 10 (range 7–24). … The cytogenetic analysis at diagnosis was present in 68/80 (85%) patients and of 19/80 (28%) had a high risk cytogenetic. At diagnosis, the most common comorbidities were: arterial hypertension ( n = 28), cardiomyopathy ( n = 10) and diabetes ( n = 1). …

Diagnosis and management of neutropenia in adults: Expert guidance.

Neutropenia in general is defined as a blood neutrophil count of less than 1.5 × 109/L, in severe neutropenia counts drop to less than 0.5 × 109/L, but the definition of neutropenia varies according to the patient's ethnic origin and age. For Caucasian adults, the absolute neutrophil count (ANC) threshold of 1.8 × 109/L is adopted for the definition of neutropenia according to the World Health Organization (see Fioredda et al. (1)). It can be inherited or acquired, and it is an uncommon haematological finding in adult outpatient clinics. Neutropenia can result from decreased production of neut

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… An annual bone marrow examination with cytogenetic analysis is recommended for patients with congenital neutropenia, as well as for those with changes in blood counts or general health that suggest haematopoietic evolution to leukemia. …

Shaping the Treatment Paradigm Based on the Current Understanding of the Pathobiology of Multiple Myeloma: An Overview.

Multiple myeloma is an incurable malignancy which despite progressive improvements in overall survival over the last decade remains characterised by recurrent relapse with progressively shorter duration of response and treatment-free intervals with each subsequent treatment. Efforts to unravel the complex and heterogeneous genomic alterations, the marked dysregulation of the immune system and the multifarious interplay between malignant plasma cells and those of the tumour microenvironment have not only led to improved understanding of myelomagenesis and disease progression but have facilitate

Проверка корейского инструмента гериатрической оценки у пожилых пациентов с множественной миеломой: многоцентральное исследование.

Цель Это исследование дает оценку корейской группе по изучению раковых заболеваний Score-7 (В тыс.KG-7) эффективность инструмента скрининга для пожилых пациентов с множественными миеломой (ММ) в целях предотвращения недосмотра и чрезмерной обработки. 100 Пожилые пациенты 70 и старше с недавно поставленным диагнозом MM, которые не прошли трансплантации с августа 2020 по январь 2022Средний возраст 77 годы и 73.0% Число пациентов, отнесенных к категории на этапах Международной системы уплотнения 2 или 3. Использование a 5-point отсечение KG-7 индекс (нежелезнодорожный, балл) ≥ 5Экспериментальное

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, b

Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.

The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML). AML with adverse genetic factors uniformly shows resistance to standard chemotherapy and is associated with poor prognosis. Here, we focus on the biological background and real-world etiology of these adverse genetic factors and then describe a strategy to overcome the clinical disadvantages in terms of targeting pivotal molecular mechanisms. Different adverse genetic factors often rely on common pathways. KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma.

We conducted a phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone (KPd) and KPd with daratumumab (Dara-KPd) in relapsed/refractory multiple myeloma. The primary end points were identification of a maximum tolerated dose (MTD) of KPd for phase 1, and rates of overall response (ORR) and near complete response (nCR) after 4 cycles of KPd and Dara-KPd, respectively, for phase 2. The MTD for KPd was carfilzomib 20/27 mg/m2 on days 1, 2, 8, 9, 15, and 16 (cycles 1-8) and days 1, 2, 15, and 16 for cycles 9 and beyond; oral pomalidomide 4 mg on days 1 to 21; and oral dexamethasone 40 mg w

Teclistamab versus real-world physician's choice of therapy in triple-class exposed relapsed/refractory multiple myeloma.

Aim: We compared the effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC) in triple-class exposed relapsed/refractory multiple myeloma. Materials & methods: MajesTEC-1 eligibility criteria were applied to the RWPC cohort. Baseline covariate imbalances were adjusted using inverse probability of treatment weighting. Overall survival, progression-free survival and time to next treatment were compared. Results: After inverse probability of treatment weighting, baseline characteristics were similar between cohorts (teclistamab, n = 165; RWPC, n = 364 [766 observations

Исключительные долгосрочные ответные меры, принятые в ходе испытаний ОКЕАН и ГОРИЗОН: мелфлюфен-дексаметасон в качестве расширения возможностей лечения повторной/нереакторной множественной миеломы в эпоху новой иммунотерапии?

Алкилатные агенты представляют собой первый эффективный класс наркотиков в множестве миеломы (ММ), но после внедрения новых эффективных лекарственных средств их потребление постепенно сокращается и в настоящее время переводится на автологическую трансплантацию стволовых клеток (ASCT) и несколько других объектов. Тем не менее, США одобрили комбинацию мелфлюфена (пиптидно-наркотика, про-наркотика мелфалана) и дексаметасона. Управление по контролю за продуктами питания и лекарственными препаратами (УПП) для пациентов с трехклассными отклонениями после ≥ 4 :: предыдущая терапия (ЛОТ) по результата

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… Baseline cytogenetic analysis showed the presence of hyperdiploid karyotype and absence of HR chromosomal abnormalities; ISS was III and Revised-ISS (R-ISS) was II. …

Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.

BackgroundRearrangements of the histone-lysine-N-methyltransferase (KMT2A), previously referred to as mixed-lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A-rearranged (KMT2A-r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non-KMT2A-r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KM

Multiple Myeloma in 2023 Ways: From Trials to Real Life.

Multiple myeloma is a chronic hematologic malignancy that obstinately tends to relapse. Basic research has made giant strides in better characterizing the molecular mechanisms of the disease. The results have led to the manufacturing of new, revolutionary drugs which have been widely tested in clinical trials. These drugs have been approved and are now part of the therapeutic armamentarium. As a consequence, it is essential to combine what we know from clinical trials with real-world data in order to improve therapeutic strategies. Starting with this premise, our review aims to describe the cu

Unravelling Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treatment in Real-World Practice in Spain: The CARINAE Study.

Real-world evidence on the impact of monoclonal antibodies as first-line treatment in Spain is limited. This observational, retrospective and prospective, multicenter, descriptive study included 117 transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients divided into Group A, who received no daratumumab standard regimens, and the DVMP group (daratumumab, bortezomib, melphalan, and prednisone treatment). More than 90% of the patients in Group A received bortezomib, lenalidomide, or a combination of them. The median follow-up time for Group A was 38.2 months in comparison to 2

A New Paradigm for Pediatric AML: Improving the Pipeline for Treatments Targeting Cytogenetic and Molecular Alterations.

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where "one-size-fits-all" chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on s

Response rates and minimal residual disease outcomes as potential surrogates for progression-free survival in newly diagnosed multiple myeloma.

Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) were performed to identify randomized cli