Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study.

Abstract:

:Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.

journal_name

Blood

journal_title

Blood

authors

Sanchorawala V,Sarosiek S,Schulman A,Mistark M,Migre ME,Cruz R,Sloan JM,Brauneis D,Shelton AC

doi

10.1182/blood.2019004436

subject

Has Abstract

pub_date

2020-04-30 00:00:00

pages

1541-1547

issue

18

eissn

0006-4971

issn

1528-0020

pii

440750

journal_volume

135

pub_type

杂志文章

相关文献

BLOOD文献大全
  • A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo.

    abstract::For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-03-1193

    authors: Gunzer M,Weishaupt C,Hillmer A,Basoglu Y,Friedl P,Dittmar KE,Kolanus W,Varga G,Grabbe S

    更新日期:2004-11-01 00:00:00

  • Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes.

    abstract::Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with biologic effects that include regulation of hematopoietic stem cell development, extracellular matrix remodeling, and inflammatory cytokine generation. To delineate the potential role of VEGF in patients with myelodysplastic syndrome (MDS), ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.5.1427

    authors: Bellamy WT,Richter L,Sirjani D,Roxas C,Glinsmann-Gibson B,Frutiger Y,Grogan TM,List AF

    更新日期:2001-03-01 00:00:00

  • Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis.

    abstract::Lipoprotein (a) [Lp(a)] has been associated with both anti-fibrinolytic and atherogenic effects. However, no direct link currently exists between this atherogenic lipoprotein and intravascular coagulation. The current study examined the binding and functional effects of Lp(a), its lipoprotein constituents, apoliprotei...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.10.2980

    authors: Caplice NM,Panetta C,Peterson TE,Kleppe LS,Mueske CS,Kostner GM,Broze GJ Jr,Simari RD

    更新日期:2001-11-15 00:00:00

  • Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures.

    abstract::Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted preprocedure, whether bridging therapy was ...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2014-08-595496

    authors: Garcia D,Alexander JH,Wallentin L,Wojdyla DM,Thomas L,Hanna M,Al-Khatib SM,Dorian P,Ansell J,Commerford P,Flaker G,Lanas F,Vinereanu D,Xavier D,Hylek EM,Held C,Verheugt FW,Granger CB,Lopes RD

    更新日期:2014-12-11 00:00:00

  • The kringle stabilizes urokinase binding to the urokinase receptor.

    abstract::The structural basis of the interaction between single-chain urokinase-type plasminogen activator (scuPA) and its receptor (uPAR) is incompletely defined. Several observations indicated the kringle facilitates the binding of uPA to uPAR. A scuPA variant lacking the kringle (Delta K-scuPA) bound to soluble uPAR (suPAR)...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-03-0949

    authors: Bdeir K,Kuo A,Sachais BS,Rux AH,Bdeir Y,Mazar A,Higazi AA,Cines DB

    更新日期:2003-11-15 00:00:00

  • Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia.

    abstract::A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated ad...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dührsen U,Uppenkamp M,Uppenkamp I,Becher R,Engelhard M,König E,Meusers P,Meuer S,Brittinger G

    更新日期:1986-08-01 00:00:00

  • Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia.

    abstract::Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-04-085969

    authors: Kebriaei P,Detry MA,Giralt S,Carrasco-Yalan A,Anagnostopoulos A,Couriel D,Khouri IF,Anderlini P,Hosing C,Alousi A,Champlin RE,de Lima M

    更新日期:2007-11-01 00:00:00

  • Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease.

    abstract::The incidence and severity of acute graft-versus-host disease (GVHD) after allogeneic transplantation using peripheral blood progenitor cells mobilized by granulocyte colony-stimulating factor (G-CSF) appear to be no worse than those after bone marrow transplantation, despite the presence of large numbers of T cells i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Pan L,Delmonte J Jr,Jalonen CK,Ferrara JL

    更新日期:1995-12-15 00:00:00

  • Nonsteroidal anti-inflammatory drugs inhibit a Fyn-dependent pathway coupled to Rac and stress kinase activation in TCR signaling.

    abstract::In addition to their anti-inflammatory properties, nonsteroidal anti-inflammatory drugs (NSAIDs) harbor immunosuppressive activities related to their capacity both to inhibit cyclooxygenases (COXs) and to act as peroxisome proliferator-activated receptor (PPAR) ligands. We have previously shown that the stress-activat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-04-1299

    authors: Paccani SR,Patrussi L,Ulivieri C,Masferrer JL,D'Elios MM,Baldari CT

    更新日期:2005-03-01 00:00:00

  • Leukotriene B4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells.

    abstract::Biosynthesis of leukotrienes (LTs) occurs in human myeloid cells and B lymphocytes. However, the function of leukotrienes in B lymphocytes is unclear. Here, we report that B-cell chronic lymphocytic leukemia (B-CLL) cells produce leukotriene B(4), and that specific leukotriene biosynthesis inhibitors counteracted CD40...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-07-2546

    authors: Runarsson G,Liu A,Mahshid Y,Feltenmark S,Pettersson A,Klein E,Björkholm M,Claesson HE

    更新日期:2005-02-01 00:00:00

  • Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.

    abstract::Atypical hemolytic uremic syndrome (aHUS) is a severe renal disease that is associated with defective complement regulation caused by multiple factors. We previously described the deficiency of factor H-related proteins CFHR1 and CFHR3 as predisposing factor for aHUS. Here we identify in an extended cohort of 147 aHUS...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-09-109876

    authors: Józsi M,Licht C,Strobel S,Zipfel SL,Richter H,Heinen S,Zipfel PF,Skerka C

    更新日期:2008-02-01 00:00:00

  • Unmaintained remissions in multiple myeloma.

    abstract::Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmus...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Alexanian R,Gehan E,Haut A,Saiki J,Weick J

    更新日期:1978-06-01 00:00:00

  • Cell-surface expression of RhD blood group polypeptide is posttranscriptionally regulated by the RhAG glycoprotein.

    abstract::In most cases, the lack of Rh in Rh(null) red cells is associated with RHAG gene mutations. We explored the role of RhAG in the surface expression of Rh. Nonerythroid HEK293 cells, which lack Rh and RhAG, or erythroid K562 cells, which endogenously express RhAG but not Rh, were transfected with RhD and/or RhAG cDNAs u...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Mouro-Chanteloup I,D'Ambrosio AM,Gane P,Le Van Kim C,Raynal V,Dhermy D,Cartron JP,Colin Y

    更新日期:2002-08-01 00:00:00

  • Interleukin-1, tumor necrosis factor, and the production of colony-stimulating factors by cultured mesenchymal cells.

    abstract::Although the genes for four hematopoietic colony-stimulating factors (CSFs) have been cloned, neither the mechanism of the regulation of their production nor their cellular origins have been established with certainty. Monocytes are known to produce colony-stimulating and burst-promoting activities, as well as several...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sieff CA,Niemeyer CM,Mentzer SJ,Faller DV

    更新日期:1988-10-01 00:00:00

  • How I conduct a comprehensive chronic graft-versus-host disease assessment.

    abstract::Since the National Institutes of Health Chronic Graft-Versus-Host Disease (cGVHD) Consensus Project in 2005, a need has emerged to evaluate cGVHD more methodically, not only to make a cGVHD diagnosis, but also to accurately classify individual organ and global organ severity, at baseline and in follow-up so that subje...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-04-314815

    authors: Carpenter PA

    更新日期:2011-09-08 00:00:00

  • Murine myeloproliferative disorder as a consequence of impaired collaboration between dendritic cells and CD4 T cells.

    abstract::Dendritic cells (DCs) are a key cell type in the initiation of the adaptive immune response. Recently, an additional role for DCs in suppressing myeloproliferation was discovered. Myeloproliferative disorder (MPD) was observed in murine studies with constitutive depletion of DCs, as well as in patients with congenital...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2018-05-850321

    authors: Humblet-Baron S,Barber JS,Roca CP,Lenaerts A,Koni PA,Liston A

    更新日期:2019-01-24 00:00:00

  • Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies.

    abstract::We present a programmable bioengineered 3-dimensional silk-based bone marrow niche tissue system that successfully mimics the physiology of human bone marrow environment allowing us to manufacture functional human platelets ex vivo. Using stem/progenitor cells, megakaryocyte function and platelet generation were recor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-08-595561

    authors: Di Buduo CA,Wray LS,Tozzi L,Malara A,Chen Y,Ghezzi CE,Smoot D,Sfara C,Antonelli A,Spedden E,Bruni G,Staii C,De Marco L,Magnani M,Kaplan DL,Balduini A

    更新日期:2015-04-02 00:00:00

  • Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice.

    abstract::Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and adenosine triphosphate s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-03-492504

    authors: Kim K,Hahm E,Li J,Holbrook LM,Sasikumar P,Stanley RG,Ushio-Fukai M,Gibbins JM,Cho J

    更新日期:2013-08-08 00:00:00

  • Detection of Epstein-Barr virus messenger RNA in Reed-Sternberg cells of Hodgkin's disease by in situ hybridization with biotinylated probes on specially processed modified acetone methyl benzoate xylene (ModAMeX) sections.

    abstract::Microscopic intracellular detection of Epstein-Barr virus (EBV) messenger RNA in Reed-Sternberg cells of Hodgkin's disease (HD) was possible by in situ hybridization, in tissue sections prepared by a method termed modified acetone methyl benzoate xylene (ModAMeX). The ModAMeX method was initially developed for simulta...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Brousset P,Chittal S,Schlaifer D,Icart J,Payen C,Rigal-Huguet F,Voigt JJ,Delsol G

    更新日期:1991-04-15 00:00:00

  • Anticonvulsant-induced aplastic anemia: increased susceptibility to toxic drug metabolites in vitro.

    abstract::A 53-yr-old man sequentially developed aplastic anemia from phenytoin and carbamazepine. Both compounds undergo metabolism to potentially toxic arene oxide intermediates. We tested the hypothesis that the patient's adverse reactions were due to a defect in detoxification of such metabolites by challenging his peripher...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gerson WT,Fine DG,Spielberg SP,Sensenbrenner LL

    更新日期:1983-05-01 00:00:00

  • Utilization of a continuous flow reactor to study the lipoprotein-associated coagulation inhibitor (LACI) that inhibits tissue factor.

    abstract::A microperfusion system containing a glass capillary, the inner surface of which is coated with a phospholipid bilayer containing tissue factor, was used to explore the requirement for factors VIIa and Xa in the complex formed with the lipoprotein-associated coagulation inhibitor (LACI). Various combinations of factor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gemmell CH,Broze GJ Jr,Turitto VT,Nemerson Y

    更新日期:1990-12-01 00:00:00

  • HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients.

    abstract::Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective stud...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2010-10-316083

    authors: Zerr DM,Fann JR,Breiger D,Boeckh M,Adler AL,Xie H,Delaney C,Huang ML,Corey L,Leisenring WM

    更新日期:2011-05-12 00:00:00

  • Structural integrity of the glycoprotein IIb and IIIa genes in Glanzmann thrombasthenia patients from Israel.

    abstract::Glanzmann thrombasthenia is an autosomal recessive disorder of the platelet glycoproteins (GP) IIb and IIIa. These glycoproteins normally serve as receptors for other adhesive glycoproteins, including fibrinogen, von Willebrand factor, and fibronectin. Most patients affected by Glanzmann thrombasthenia have low levels...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Russell ME,Seligsohn U,Coller BS,Ginsberg MH,Skoglund P,Quertermous T

    更新日期:1988-11-01 00:00:00

  • p53 abnormalities in splenic lymphoma with villous lymphocytes.

    abstract::The incidence and role of p53 abnormalities have not been reported in splenic lymphoma with villous lymphocytes (SLVL), the leukemic counterpart of splenic marginal zone lymphoma. Because p53 abnormalities correlate with progressive and refractory disease in cancer and isochromosome 17q has been described in SLVL, a l...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.11.3552

    authors: Gruszka-Westwood AM,Hamoudi RA,Matutes E,Tuset E,Catovsky D

    更新日期:2001-06-01 00:00:00

  • The ASH Choosing Wisely® campaign: five hematologic tests and treatments to question.

    abstract::Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-07-518423

    authors: Hicks LK,Bering H,Carson KR,Kleinerman J,Kukreti V,Ma A,Mueller BU,O'Brien SH,Pasquini M,Sarode R,Solberg L Jr,Haynes AE,Crowther MA

    更新日期:2013-12-05 00:00:00

  • Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation.

    abstract::Donor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic mal...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2005-04-1614

    authors: Pavletic SZ,Carter SL,Kernan NA,Henslee-Downey J,Mendizabal AM,Papadopoulos E,Gingrich R,Casper J,Yanovich S,Weisdorf D,National Heart, Lung, and Blood Institute Unrelated Donor Marrow Transplantation Trial.

    更新日期:2005-11-01 00:00:00

  • In vivo stem cell function of interleukin-3-induced blast cells.

    abstract::The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, we obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells b...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tsunoda J,Okada S,Suda J,Nagayoshi K,Nakauchi H,Hatake K,Miura Y,Suda T

    更新日期:1991-07-15 00:00:00

  • Increased death receptor resistance and FLIPshort expression in polycythemia vera erythroid precursor cells.

    abstract::Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by excessive erythrocyte production. Most patients with PV harbor an activating JAK2 mutation, but the molecular links between this mutation and erythrocyte overproduction are unknown. The interaction between death receptors and their ligands...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-07-3037

    authors: Zeuner A,Pedini F,Signore M,Ruscio G,Messina C,Tafuri A,Girelli G,Peschle C,De Maria R

    更新日期:2006-05-01 00:00:00

  • Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis.

    abstract::Cytomegalovirus (CMV) has been a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). The importance of the recipient's serologic status is paramount. However, the importance of the donor's serologic status in CMV-seropositive recipients is controversial. We analyzed the influence o...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-10-3263

    authors: Ljungman P,Brand R,Einsele H,Frassoni F,Niederwieser D,Cordonnier C

    更新日期:2003-12-15 00:00:00

  • Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses.

    abstract::The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-07-2283

    authors: Li HY,Appelbaum FR,Willman CL,Zager RA,Banker DE

    更新日期:2003-05-01 00:00:00