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1.
Br J Haematol ; 192(5): 843-852, 2021 03.
Article in English | MEDLINE | ID: mdl-32780894

ABSTRACT

Deletion of the long arm of chromosome 6 (del6q) is the most frequent cytogenetic abnormality in Waldenström macroglobulinaemia (WM), occurring in approximately 50% of patients. Its effect on patient outcome has not been completely established. We used fluorescence in situ hybridisation to analyse the prevalence of del6q in selected CD19+ bone marrow cells of 225 patients with newly diagnosed immunoglobulin M (IgM) monoclonal gammopathies. Del6q was identified in one of 27 (4%) cases of IgM-monoclonal gammopathy of undetermined significance, nine of 105 (9%) of asymptomatic WM (aWM), and 28/93 (30%) of symptomatic WM (sWM), and was associated with adverse prognostic features and higher International Prognostic Scoring System for WM (IPSSWM) score. Asymptomatic patients with del6q ultimately required therapy more often and had a shorter time to transformation (TT) to symptomatic disease (median TT, 30 months vs. 199 months, respectively, P < 0·001). When treatment was required, 6q-deleted patients had shorter progression-free survival (median 20 vs. 47 months, P < 0·001). The presence of del6q translated into shorter overall survival (OS), irrespective of the initial diagnosis, with a median OS of 90 compared with 131 months in non-del6q patients (P = 0·01). In summary, our study shows that del6q in IgM gammopathy is associated with symptomatic disease, need for treatment and poorer clinical outcomes.


Subject(s)
Cell Transformation, Neoplastic/genetics , Waldenstrom Macroglobulinemia/genetics , Aged , Asymptomatic Diseases , Bone Marrow Cells/chemistry , Bone Marrow Cells/ultrastructure , Chromosome Deletion , Chromosomes, Human, Pair 6/genetics , Female , Humans , Immunoglobulin M/blood , Immunophenotyping , In Situ Hybridization, Fluorescence , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/genetics , Paraproteins/analysis , Prognosis , Progression-Free Survival , Risk Assessment , Survival Analysis , Time Factors , Treatment Outcome , Waldenstrom Macroglobulinemia/pathology
2.
Expert Opin Drug Saf ; 17(6): 609-621, 2018 06.
Article in English | MEDLINE | ID: mdl-29768934

ABSTRACT

INTRODUCTION: Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the Bruton Tyrosine Kinase (BTK) inhibitors. AREAS COVERED: Two main therapeutic attitudes are possible: (1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies or (2) new approaches with BTK inhibitors, usually alone. Other possibilities such as BCL2 inhibitors, PI3K/AKT inhibitors, and others are currently under evaluation, but we will focus the review on the most consolidated approaches that are available for patients with WM at different stages of the disease. PubMed, Web of Science, and clinicaltrials.gov were queried for the keywords 'Waldenstrom macroglobulinemia' and the different drugs here evaluated through 1 February 2018. EXPERT OPINION: Although WM has no many specific drugs, there are many possible therapies, including Ibrutinib, the first formally approved drug for this disorder.


Subject(s)
Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Waldenstrom Macroglobulinemia/drug therapy , Agammaglobulinaemia Tyrosine Kinase , Animals , Drug Approval , Drug Design , Humans , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology , Waldenstrom Macroglobulinemia/physiopathology
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