Waldenstrom's macroglobulinemia front line treatment.
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ABSTRACT:
SUBMITTER: Tedeschi A
PROVIDER: S-EPMC8925655 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Waldenström's macroglobulinemia front line treatment.
Tedeschi Alessandra A Frustaci Anna Maria AM
HemaSphere 20190630 Suppl
Similar Datasets
Project description:Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma with indolent course and prolonged disease course. The first-in-class Bruton's tyrosine kinase inhibitor, ibrutinib, has shown significant activity and a distinct adverse event profile among both newly diagnosed and relapsed/refractory WM patients. Interestingly, clinical responses to ibrutinib have been shown to be dependent on patients' MYD88 and CXCR4 mutational status. The recent outcomes of the Phase III iNNOVATE trial showed that the combination of ibrutinib with rituximab resulted in a significantly prolonged progression-free survival compared with rituximab monotherapy, which provides a novel therapeutic option in the clinical practice especially for the rituximab-refractory WM patients. However, the need for continuous drug administration along with the unique toxicity manifestations may render the patient management challenging. Furthermore, our understanding of the underlying resistant mechanisms to ibrutinib is currently being evolved.
| S-EPMC6717707 | biostudies-literature
Project description:The diagnosis of Waldenström's macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström's Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests, and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.
| S-EPMC9898035 | biostudies-literature
Project description: Not available
| S-EPMC8925683 | biostudies-literature
Project description:Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5-, CD10-, CD19+, CD20+ and CD23-. Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa-associated lymphoid tissue (MALT) lymphoma must be excluded. Weakness or fatigue from anemia, fever, night sweats, or weight loss represent the most common symptoms. Hepatosplenomegaly may be a major feature. Anemia, thrombocytopenia, hyperviscosity or peripheral neuropathy may be prominent features. Systemic amyloidosis, renal insufficiency and cryoglobulinemia may also be seen. WM must be differentiated from smoldering Waldenström's Macroglobulinemia (SWM) which is an intermediate disease state characterized by an IgM protein ≥3 g/dL and/or a bone marrow containing ≥10% bone marrow lymphoplasmacytic infiltration but no end-organ damage such as symptomatic anemia, constitutional symptoms, hyperviscosity, symptomatic hepatosplenomegaly or lymphadenopathy.
| S-EPMC5117990 | biostudies-other
Project description:Bruton's tyrosine kinase (BTK) inhibition is one of the treatment standards for patients with relapsed/refractory Waldenström's macroglobulinemia (WM) and for patients with WM who are unsuitable for immunochemotherapy (ICT). It offers deep and durable responses with a manageable safety profile that is generally favorable compared with ICT regimens. However, the limitations of the first approved BTK inhibitor (BTKi), ibrutinib, include reduced efficacy in patients lacking the characteristic WM mutation (MYD88L265P) and toxicities related to off-target activity. The risk of atrial fibrillation (AF) and other cardiovascular side effects are a notable feature of ibrutinib therapy. Several next-generation covalent BTKis with greater selectivity for BTK are at various stages of development. In November 2021, zanubrutinib became the first of these agents to be approved by the European Medicines Agency for the treatment of WM. Head-to-head trial data indicate that it has comparable efficacy to ibrutinib for patients with WM overall, although it may be more effective in patients with CXCR4 mutations or wild-type MYD88. In the clinical trial setting, its greater selectivity translates into a reduced risk of cardiovascular side effects, including AF. Acalabrutinib, which is pre-approval in WM, appears to offer similar advantages over ibrutinib in terms of its safety profile. Beyond the next-generation covalent BTKis, non-covalent BTKis are an emerging class with the potential to provide a therapeutic option for patients who relapse on covalent BTKis. In the future, BTKis may be increasingly utilized within combination regimens. Several ongoing trials in WM are investigating the potential for BTKi use in combination with established and novel targeted agents.
| S-EPMC9883164 | biostudies-literature
Project description:Waldenstrom's macroglobulinemia (WM) is very distinct from other indolent lymphoma subtypes: by definition it is accompanied by a monoclonal IgM gammopathy; it presents always with bone marrow infiltration and often with clinical symptoms such as neuropathy or hyperviscosity. These disease characteristics and the frequently advanced age of the WM patient pose a major challenge to the treating clinician even today. Recently, there has been not only substantial progress in our understanding of the biology of WM, but we have also significantly improved our tools to prognostify and to treat patients with this disease. This review summarizes our current knowledge about WM and aims at offering a guideline for the clinical management of patients with this lymphoma subtype, covering questions on how to manage diagnosis, prognostification and treatment based on the most recent data.
| S-EPMC3626020 | biostudies-other
Project description:IntroductionTreatment options for Waldenström's Macroglobulinemia (WM) have expanded rapidly in the last decades. However, there is no consensus on a preferred treatment. Therefore, patient preferences become increasingly important in making individualized treatment plans. Still, WM patients' priorities and perspectives regarding their treatment options are unknown. We evaluated treatment preferences of WM patients using a discrete choice experiment (DCE).MethodsA mixed-method approach was utilized for identification and selection of attributes/levels. The DCE questionnaire included five attributes: type of agent (targeted versus chemotherapy); frequency and route of administration; 5-year progression-free survival (PFS); adverse events; and risk of secondary malignancies. An orthogonal design and a mixed logit panel data model were used to construct choice tasks and assess patient preferences, respectively.ResultsThree hundred thirty WM patients participated in the project. In total, 214 (65%) complete questionnaires were included for data analysis. The 5-year PFS, followed by risk of secondary malignancies were the most important attributes for making treatment choices. Regarding side effects, patients chose to avoid neuropathy the most compared to nausea/vomiting and extreme fatigue. Patients preferred a fixed-duration treatment with IV/SC administration at the hospital over a continuous daily oral regimen at home.ConclusionThese are the first systematic data obtained on WM patient preferences for treatment. The results may help discussions with individual patients about their treatment choices. Also, these data can help design clinical trials in WM and inform health-care decision-making regarding outcomes that are most relevant to patients.
| S-EPMC9939214 | biostudies-literature
Project description:Monoclonal antibodies have established an important role in the treatment armamentarium of hematological malignancies, including Waldenström's macroglobulinemia. Rituximab, an anti-CD20 monoclonal antibody, is established as standard therapy for this unique low grade lymphoma, due to its effectiveness and safety as monotherapy, in combination with chemotherapy or other targeted therapies in WM. Newer monoclonal antibodies, targeting CD20 or other surface antigens, have shown to be effective in patients with WM. In the current review we attempt to provide an overview of the mechanisms of action of monoclonal antibodies and discuss clinical evidence that support their use in WM and their therapeutic potential.
| S-EPMC9098391 | biostudies-literature
Project description:CXCR4 cDNA transcripts were subcloned into plenti-IRES-GFP vectors, and stably transduced using a lentiviral system In addition to wild-type CXCR4, vectors with the mutations c.1013C>G (p.Ser338*), c.932_933insT (p.Thr311fs), and c.1030_1041delinsGT (p.Ser344fs) were generated. Cell lines were stimulated with 50nM of the CXCR4 ligand CXCL12 (SDF1A) (R&D Systems, Minneapolis MN) for two hours. RNA from each sample was extracted at baseline and at 2 hours.
2016-06-10 | GSE83150 | GEO
Project description:Waldenström’s macroglobulinemia (WM) is a distinct clinicobiological entity defined as a B-cell neoplasm characterized by a lymphoplasmacytic infiltrate in the bone marrow and immunoglobulin M paraprotein production. Cytogenetic analysis is limited by the difficulty in obtaining tumor metaphases and the genetic basis of the disease remains poorly defined. We performed a comprehensive analysis in 42 WM patients by using high-resolution array-based comparative genomic hybridization with the Human Genome 244A microarray. Overall, 83% of samples have chromosomal abnormalities, with a median of three abnormalities per patient (range 0 to 27). The most common abnormality was 6q deletion (40%) and four non-overlapped minimal deleted regions (MDR) were identified. Gain of 6p was the second most common abnormality (17%) and its presence was always concomitant with 6q loss. An interstitial MDR was delineated at 13q14 including MIRN15A and MIRN16-1 in 10% of patients. Other recurrent deletions were 7q22, 8p, 11q22-q23, 11q23-q24 and 17p11-p13 (7% each). Copy gains were identified in chromosomes 18 (17%), 4 (12%), 3 (10%), 8q (10%) and Xq27.1-q28 (10%). To note, we reported biallelic deletions and/or inactivating mutations with uniparental disomy in TRAF3 and TNFAIP3, two negative regulators of the NF-kB signaling pathway. Furthermore, we confirmed the association between TRAF3 inactivation and increased transcriptional activity of NF-kB target genes. Mutational activation of the NF-kB pathway, which is normally activated by ligand-receptor interactions within the bone marrow microenvironment, highlight its biologic importance, and suggest a therapeutic role for inhibitors of NF-KB pathway activation in the treatment of Waldenström’s macroglobulinemia. Keywords: gene expression profiling; array comparative genomic hybridization
2009-08-24 | GSE12668 | GEO