Abstract:
:The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents. Whilst resistance mechanisms have been best studied for proteasome inhibitors, particularly bortezomib, class effects do not universally apply to all class members, and within-class differences in efficacy, toxicity and resistance mechanisms have been observed. Although immunomodulatory agents share the common cellular target cereblon and thus resistance patterns relate to cereblon expression, the unique cell surface antigens to which monoclonal antibodies are directed means these agents frequently exhibit unique within-class differences in clinical efficacy and resistance patterns. This review describes the major classes of novel therapies for myeloma, highlights the major clinical trials within each class and discusses known resistance mechanisms.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Wallington-Beddoe CT,Sobieraj-Teague M,Kuss BJ,Pitson SMdoi
10.1111/bjh.15210subject
Has Abstractpub_date
2018-07-01 00:00:00pages
11-28issue
1eissn
0007-1048issn
1365-2141journal_volume
182pub_type
杂志文章,评审abstract::Epistaxis is a common problem amongst anti-coagulated patients. Application of first-aid principles can control the majority of bleeds. In our sample of 60 patients attending the anticoagulant clinic, 40% were unable to think of a single measure that would be helpful in controlling a nose bleed. 6 weeks after being gi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1865.x
更新日期:1996-10-01 00:00:00
abstract::Neutrophil hypersegmentation (NH) is an important haematological feature of cobalamin or folate deficiency. As iron deficiency and folate deficiency often occur in the same target groups it is important to establish whether iron deficiency alone is a cause of NH. We report a case-control study which addresses this iss...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01756.x
更新日期:1999-12-01 00:00:00
abstract::Red cell membrane proteins have been examined in a family in which three children have severe transfusion-dependent homozygous hereditary elliptocytosis. The membranes in all three show a considerable excess of spectrin dimers over tetramers in spectrin extracts. The red cell membranes of their parents with heterozygo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1983.tb02085.x
更新日期:1983-06-01 00:00:00
abstract::Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 ...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2008.07370.x
更新日期:2008-11-01 00:00:00
abstract::Activating mutations of NOTCH1 are a common occurrence in T-cell acute lymphoblastic leukaemia (T-ALL), but its impact on T-ALL treatment is still controversial. In this study, the incidence, clinical features, and prognosis of 92 Chinese children with T-ALL treated using the Beijing Children's Hospital-2003 and Chine...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12866
更新日期:2014-07-01 00:00:00
abstract::FLT3-internal tandem duplication (ITD) mutations are heterogeneous with regards to length and proportion of DNA harbouring the mutation and the expression level of FLT3 also varies widely, however very little is known about the biological effects of these variables. We studied FLT3-associated biological parameters in ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07901.x
更新日期:2009-12-01 00:00:00
abstract::Human intravenous immunoglobulin (IVIg) and anti-D immunoglobulin preparations are used in the treatment of immune thrombocytopenic purpura (ITP). One mechanism proposed to explain their therapeutic effects in ITP patients is the induction of expression of anti-inflammatory cytokines, such as interleukin (IL)-10 or IL...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06495.x
更新日期:2007-03-01 00:00:00
abstract::In an attempt to compare the sensitivity of bone radiographs and bone marrow magnetic resonance (MR) imaging for bone lesion detection in patients with stage III multiple myeloma (MM) and to evaluate the possible consequences of the replacement of the conventional radiographic skeletal survey (RSS) by an MR survey of ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01529.x
更新日期:1999-07-01 00:00:00
abstract::Lymphoproliferative diseases of large granular lymphocytes (LDGL) may arise from either CD3+ T cells or CD3- natural killer (NK) cells. LDGL with clonal proliferation of large granular lymphocytes (LGL) is defined as LGL leukaemia. The number of patients with NK-LGL leukaemia reported is limited and the pathogenesis o...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01109.x
更新日期:1998-12-01 00:00:00
abstract::Gaucher disease (GD) is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase (GluCerase) that leads to glucosylceramide (GluCer) accumulation. We previously demonstrated the existence of imbalances in certain lymphocyte populations in GD patients. We now show that GluCerase-deficient mono...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.2005.05503.x
更新日期:2005-06-01 00:00:00
abstract::We report a case of positive Philadelphia chromosome adult acute lymphoblastic leukaemia with a novel unbalanced translocation t(17;19), leading to trisomy of 17q21-qter. The patient did not obtain complete haematological response and died a few months after diagnosis. The significance of the 17q21-qter trisomy, resul...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03846.x
更新日期:2002-11-01 00:00:00
abstract::Well-established histopathological prognostic factors are lacking in primary central nervous system (CNS) lymphomas (PCNSL). The present study investigated the presence and prognostic role of tumour necrosis (TN) and reactive perivascular T-cell infiltrate (RPVI), defined as a rim of small reactive T-lymphocytes occur...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2007.06661.x
更新日期:2007-08-01 00:00:00
abstract::Mutations of Runt-related transcription factor 1 (RUNX1) have been detected in patients with myelodysplastic syndrome (MDS). However, the prognostic implication of RUNX1 mutations in primary MDS is limited. The stage of the disease at which the mutations are acquired and whether they persist during the disease course ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06811.x
更新日期:2007-11-01 00:00:00
abstract::We report our long-term experience with autologous bone marrow transplantation (ABMT) for 32 adult patients with acute lymphocytic leukaemia (ALL) in second or later remission (CR), or in first CR but with high-risk. Bone marrow was purged with mafosfamide (n = 25) or with immunomagnetic beads and monoclonal antibodie...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02634.x
更新日期:2001-03-01 00:00:00
abstract::Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::beta2-glycoprotein I (beta2GPI) bears the epitope(s) for autoimmune anticardiolipin antibodies (aCL) frequently present in patients with antiphospholipid syndrome (APS). beta2GPI is involved in coagulation and fibrinolytic systems, including inhibition of contact activation. Coagulation factor XII is an initiator of i...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03928.x
更新日期:2002-12-01 00:00:00
abstract::The blood-related cancer leukaemias were the first diseases where human cancer stem cells, or leukaemic stem cells (LSC), were isolated. The haematopoietic system is one of the best tissues for investigating cancer stem cells, because the developmental hierarchy of normal blood formation is well defined. Leukaemias ca...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2005.05596.x
更新日期:2005-08-01 00:00:00
abstract::Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated wi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12763
更新日期:2014-05-01 00:00:00
abstract::Diamond-Blackfan anaemia (DBA) is a constitutional pure red cell aplasia presenting in early childhood. In some patients, neutropenia and/or thrombocytopenia have also been observed during the course of the disease. We have followed 28 patients with steroid-refractory DBA for up to 13 years with serial peripheral bloo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01796.x
更新日期:2000-01-01 00:00:00
abstract::Myelofibrosis with myeloid metaplasia (MMM) is uniquely characterized by macroscopic bone marrow stromal changes that are believed to be both reactive and cytokine mediated. Furthermore, a prognostically detrimental increase in bone marrow angiogenesis has recently been demonstrated. These observations suggest a poten...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1365-2141.2002.03443.x
更新日期:2002-05-01 00:00:00
abstract::Multiple myeloma (MM) is a plasma cell malignancy that claims thousands of lives each year and has considerable morbidity. The disease remains incurable despite recent advances in the understanding of the disease biology and the introduction of more effective drugs is needed. This study evaluated the anti-MM activity ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05946.x
更新日期:2006-03-01 00:00:00
abstract::A phase II A study was conducted to evaluate the safety and efficacy of Givinostat, a novel Histone-Deacetylases inhibitor, in patients with Polycythaemia Vera (PV, n = 12), Essential Thrombocythaemia (ET, n = 1) and Myelofibrosis (n = 16), bearing the JAK2V617F mutation. The study was approved by the local ethics com...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2010.08266.x
更新日期:2010-08-01 00:00:00
abstract::β- thalassaemia is a disorder of globin gene synthesis resulting in reduced or absent production of the β-globin chain in red blood cells. In this study, haematopoietic stem cells were isolated from the peripheral blood of six transfusion dependent β-thalassaemia patients and six healthy controls. Following 7 and 14 d...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13432
更新日期:2015-07-01 00:00:00
abstract::Inhibitor formation in patients with haemophilia receiving factor VIII (FVIII) concentrate is a common problem requiring tolerance induction therapy. Immune tolerance is dependent on defective T cell/antigen-presenting cell (APC) interactions and inhibitor antibody formation is associated with effective T-cell/B-cell ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01994.x
更新日期:2000-04-01 00:00:00
abstract::Combined lenalidomide and dexamethasone is a standard-of-care therapy for the treatment of older adults with multiple myeloma. Lenalidomide monotherapy has not been evaluated in newly diagnosed myeloma patients. We conducted a phase II study, evaluating a response-adapted therapy for older adults newly diagnosed with ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/bjh.15700
更新日期:2019-03-01 00:00:00
abstract::MLL rearrangements were analysed in the blood of a patient receiving chemotherapy for diffuse large B-cell lymphoma using inverse polymerase chain reaction targeting exon 12, parallel sequencing and a custom algorithm design. Of thirteen MLL rearrangements detected, five were capable of generating MLL fusion genes, in...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2012.09248.x
更新日期:2012-10-01 00:00:00
abstract::The primary immune response to a viral antigen (tick-borne encephalitis, TBE) has been determined in haemophiliacs. Twelve HIV-negative and four clinically asymptomatic, HIV-positive haemophiliacs as well as 16 age-matched healthy controls were included in the study. Antibody responses after TBE vaccination were compa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb06432.x
更新日期:1992-10-01 00:00:00
abstract::Pegfilgrastim is a pegylated form of the granulocyte-colony stimulating factor, filgrastim. Herein, we report the results of a multicentre, randomized, double-blind phase III trial comparing the efficacy and safety of pegfilgrastim with filgrastim in patients with malignant lymphoma. Patients were randomized to receiv...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bjh.14088
更新日期:2016-08-01 00:00:00
abstract::A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In gene...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.14376
更新日期:2016-12-01 00:00:00
abstract::There are no accepted methods to predict the development of platelet transfusion refractoriness (PTR) due to human leucocyte antigen (HLA)-alloimmunization. Hence, matched platelets are usually given only to patients demonstrating PTR, necessarily resulting in some ineffective random donor platelets (RDPLT) transfusio...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12369
更新日期:2013-08-01 00:00:00