Abstract:
:Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3-0·5 mg/m2 ) was administered over 2 h on days 1, 4, 8, 11; POM (3-4 mg) on days 1-21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1-10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment-related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Spencer A,Harrison S,Zonder J,Badros A,Laubach J,Bergin K,Khot A,Zimmerman T,Chauhan D,Levin N,MacLaren A,Reich SD,Trikha M,Richardson Pdoi
10.1111/bjh.14987subject
Has Abstractpub_date
2018-01-01 00:00:00pages
41-51issue
1eissn
0007-1048issn
1365-2141journal_volume
180pub_type
杂志文章,多中心研究abstract::Microcirculatory disorders are a common finding in sepsis. We have analysed the influence of two factors released in sepsis, endotoxin and tumour necrosis factor (TNF), on rheological properties of blood cells. The deformability of mixed cell suspensions, isolated erythrocytes, mononuclear cells, or polymorphonuclear ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb04643.x
更新日期:1993-01-01 00:00:00
abstract::Activities of the red cell enzymes hexokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactic dehydrogenase and aspartate aminotransferase were measured in 17 chronic haemodialysis patients receiving androgen therapy, 15 untreated chronic haemodialysis patients and 15 normal subjects. Comp...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb02269.x
更新日期:1987-02-01 00:00:00
abstract::Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.13855
更新日期:2016-02-01 00:00:00
abstract::Sources for allogeneic stem cells for patients with haematological disorders lacking a histocompatible sibling donor include matched unrelated donor (MUD) and umbilical cord blood (UCB). A total of 51 patients with haematological disorders, treated with myeloablation and transplantation with either unrelated human leu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04792.x
更新日期:2004-02-01 00:00:00
abstract::We evaluated the blood from 150 patients with primary AL-amyloidosis for circulating monoclonal plasma cells using a sensitive slide-based immunofluorescence technique. The percentage of monoclonal blood plasma cells (BPC) that were in S-phase was determined by the bromodeoxyuridine labelling index (BLI). Monoclonal B...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00583.x
更新日期:1998-02-01 00:00:00
abstract::The expression of three onc-genes, c-myc, c-myb and c-fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by "in situ" hybridization with tritium-labelled probes. A relatively large amount of m-RNA from the three onc-genes was detected in myeloblasts and promy...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb02931.x
更新日期:1986-02-01 00:00:00
abstract::Allele alphaLELY is a common low-expression allele of the erythroid spectrin SPTA1 gene. It results in the aggravated expression of hereditary elliptocytosis due to SPTA1 gene mutations occurring in trans. Allele alphaLELY contains, in particular, mutations in introns 45 and 46, both in polypyrimidine tracts, and caus...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01271.x
更新日期:1999-03-01 00:00:00
abstract::The PFA-100(R) (PFA) diagnostic system for the detection of platelet dysfunction was evaluated to determine reference ranges in a normal population. The PFA determines the primary haemostasis capacity (PHC) of anticoagulated whole blood, expressed by the system's closure time (CT). In this study the CT reference range...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01660.x
更新日期:1999-09-01 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::The proviral copy (PVC) number in peripheral blood mononuclear cells (PBMCs) of human immunodeficiency virus (HIV)-infected individuals was measured by a quantitative polymerase chain reaction (PCR) assay to determine over time the relation between the viral load and the evolution towards the disease in HIV-infected p...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb06446.x
更新日期:1992-10-01 00:00:00
abstract::The haematological and immunological characteristics of 34 healthy anti-HTLV-I antibody-positive individuals (HTLV-I carriers) in southwestern Japan were examined. No significant difference was noted between carriers and the controls in counts of RBC, WBC and the absolute number of lymphocytes. The serum IgG in the ca...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb07587.x
更新日期:1986-09-01 00:00:00
abstract::Pathogen reduction (PR) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness. We conducted a multicentre, open-label, randomized, non-inferiority trial comparing the clinical effectiveness of buffy-coat derived leukoreduced platelet co...
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/j.1365-2141.2010.08227.x
更新日期:2010-07-01 00:00:00
abstract::Peripheral blood and bone marrow mononuclear cells from 10 patients with newly diagnosed Waldenström's macroglobulinaemia were analysed for the presence of leucocyte differentiation antigens using flow cytometry. Most patients had circulating intracytoplasmic-mu cells that were positive for the B-cell specific antigen...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb04139.x
更新日期:1987-04-01 00:00:00
abstract::Restriction endonuclease analysis has been performed on the alpha and beta globin gene clusters of 57 Cypriots homozygous for beta thalassaemia, 30 with the transfusion dependent form of the condition (thalassaemia major) and 27 who are less severely affected (thalassaemia intermedia). There was a significant differen...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1983.tb02041.x
更新日期:1983-03-01 00:00:00
abstract::Canine cyclic haematopoiesis (CH) appears to be a multipotential stem cell defect, possibly due to an intrinsic marrow defect. The in vitro adherent marrow cells of the cyclic haematopoietic (CH) dog were cultured as underlayers beneath normal dog nonadherent marrow cells. The marrow granulocyte-committed colony formi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb01961.x
更新日期:1982-04-01 00:00:00
abstract::A total of 622 consecutive patients with acute promyelocytic leukaemia (APL) treated within the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group during 1989-97 have been reviewed to assess the clinical effectiveness of all-trans retinoic acid (ATRA) on the incidence of early haemorrhagic deaths ...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1365-2141.2000.01936.x
更新日期:2000-03-01 00:00:00
abstract::Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single-centre studies included sufficient patients to enable analysis of the risk ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.1262940.x
更新日期:1997-06-01 00:00:00
abstract::Iron is required for monocyte/macrophage differentiation of HL-60 leukaemia cells. Differentiation requires induction of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1), and cell cycle arrest at the G1/S checkpoint. With iron depletion, p21 induction and differentiation are blocked. To establish the roles of iro...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03498.x
更新日期:2002-06-01 00:00:00
abstract::Endothelial cells (EC) were isolated from the umbilical vein of a newborn girl with type I 'platelet low' von Willebrand disease (I vWD) and endothelial localization and release and the ability of subendothelial von Willebrand factor (vWF) to support platelet adhesion were compared with those of normal EC. vWF was det...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb04636.x
更新日期:1993-01-01 00:00:00
abstract::Persistent aplasia is a rare complication with poor prognosis after intensive chemotherapy for acute leukaemia. A 59-year-old man with acute myeloid leukaemia (AML), was treated after 186 d of chemotherapy-induced persistent aplasia with an allogeneic peripheral blood stem cell transplantation (PBSCT) from a matched u...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03742.x
更新日期:2002-08-01 00:00:00
abstract::We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 ...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2006.06489.x
更新日期:2007-03-01 00:00:00
abstract::Graft failure is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (HSCT). We report a cohort of 19 consecutive patients (median age: 8·5 years) with acute leukaemias (n = 14) and non-malignant diseases (n = 5) who experienced graft failure after previous HSCT from matched (n = ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14190
更新日期:2016-10-01 00:00:00
abstract::In this study we investigated the proliferation of three well-documented MM lines and 10 bone marrow samples from myeloma patients in response to rh-SCF alone and combined with Interleukin-6 (IL-6), IL-3 and IL-3/GM-CSF fusion protein PIXY 321. Neoplastic plasma cells were highly purified (> 90%) by immunomagnetic dep...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb05115.x
更新日期:1994-12-01 00:00:00
abstract::A single immunoglobulin light chain lambda was identified in the blast cells of two out of 12 patients with common acute lymphoblastic leukaemia (C-ALL) using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Inhibition at the cell surface proved that the reaction was a genuine anti-lambda reaction...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb06274.x
更新日期:1989-01-01 00:00:00
abstract::Red cell pyruvate kinase (PK) deficiency is the most frequent enzyme abnormality of the glycolytic pathway causing hereditary non-spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life-threatening neonatal anaemia and jaundice necessitating ex...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2005.05527.x
更新日期:2005-07-01 00:00:00
abstract::Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15086
更新日期:2018-03-01 00:00:00
abstract::The safety and efficacy of the combination clofarabine/cyclophosphamide/etoposide were evaluated in children with advanced acute lymphoblastic leukaemia (ALL). The study enrolled 25 paediatric patients (median age 12.5 years) with either refractory (n = 17; 68%) or multiple relapsed (n = 8; 32%) ALL to receive clofara...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/j.1365-2141.2009.07882.x
更新日期:2009-11-01 00:00:00
abstract::Pericardial effusion (PE) is a rare but potentially life-threatening complication for allogeneic haematopoietic stem cell transplantation (HSCT) recipients. The risk factors, aetiology, incidence and therapy are largely unclear. To investigate this issue, we reviewed 391 adult patients undergoing allogeneic HSCT betwe...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13357
更新日期:2015-06-01 00:00:00
abstract::An elderly patient with no abnormal bleeding presented with prolongation of the activated partial thromboplastin time (aPTT). Preincubation of plasma with aPTT reagent caused shortening of the abnormal clotting time. Plasma prekallikrein (PK) activity and antigen were <5 u/dL. Molecular analysis showed a homozygous Ar...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.05180.x
更新日期:2004-10-01 00:00:00
abstract::Heterozygosity for a C8524T transition in the protein C gene converting Ser270(TCG) to Leu(TTG) in the protease domain was identified in a family with venous thrombosis. The mutation was associated with parallel reduction in plasma levels of protein C anticoagulant activity and protein C antigen, which is consistent w...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02809.x
更新日期:2001-06-01 00:00:00