Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study.

Abstract:

:Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T(0) in 94 patients (44%) including ≥ partial response in 69 (32%). The median overall survival and event-free survival from T(0) were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.

journal_name

Leukemia

journal_title

Leukemia

authors

Kumar SK,Lee JH,Lahuerta JJ,Morgan G,Richardson PG,Crowley J,Haessler J,Feather J,Hoering A,Moreau P,LeLeu X,Hulin C,Klein SK,Sonneveld P,Siegel D,Bladé J,Goldschmidt H,Jagannath S,Miguel JS,Orlowski R,Palumbo A,

doi

10.1038/leu.2011.196

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

149-57

issue

1

eissn

0887-6924

issn

1476-5551

pii

leu2011196

journal_volume

26

pub_type

杂志文章,多中心研究

相关文献

LEUKEMIA文献大全
  • Localization of the chromosome 15 breakpoints and expression of multiple PML-RAR alpha transcripts in acute promyelocytic leukemia: a study of 28 Chinese patients.

    abstract::Translocation (15;17)(q22;q12-q21) is a chromosome aberration specifically found in acute promyelocytic leukemia (APL), that generates a chimeric gene between the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARA) gene, on chromosome 17. In the course of molecular investigat...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Geng JP,Tong JH,Dong S,Wang ZY,Chen SJ,Chen Z,Zelent A,Berger R,Larsen CJ

    更新日期:1993-01-01 00:00:00

  • Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs.

    abstract::Small-molecule multi-targeted cyclin-dependent kinase (CDK) inhibitors (CDKIs) are of particular interest due to their potent antitumor activity independent of p53 gene alterations. P53 deletion is associated with a very poor prognosis in multiple myeloma (MM). In this regard, we tested the anti-MM activity of RGB-286...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2013.194

    authors: Cirstea D,Hideshima T,Santo L,Eda H,Mishima Y,Nemani N,Hu Y,Mimura N,Cottini F,Gorgun G,Ohguchi H,Suzuki R,Loferer H,Munshi NC,Anderson KC,Raje N

    更新日期:2013-12-01 00:00:00

  • AKT collaborates with ERG and Gata1s to dysregulate megakaryopoiesis and promote AMKL.

    abstract::The requirement that leukemic Gata1 mutations be present in cells harboring trisomy 21 led to the discovery that overexpression of ERG drives aberrant megakaryopoiesis. Given that constitutive PI3K/AKT signaling is a frequent component of hematologic malignancies and the relationship between AKT and Notch in this line...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2013.33

    authors: Stankiewicz MJ,Crispino JD

    更新日期:2013-06-01 00:00:00

  • Molecular heterogeneity of sporadic adult Burkitt-type leukemia/lymphoma as revealed by PCR and cytogenetics: correlation with morphology, immunology and clinical features.

    abstract::Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt lymphoma but they are only found in a varying frequency in mature Burkitt-type acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2403847

    authors: Burmeister T,Schwartz S,Horst HA,Rieder H,Gökbuget N,Hoelzer D,Thiel E

    更新日期:2005-08-01 00:00:00

  • Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells.

    abstract::The cyclin-dependent kinase inhibitors known as p15, p16, p18 and p19 have been suggested as candidates for tumor suppressor genes. The main genetic alterations are deletions (bi- or monoallelic) or 5' CpG island methylation of p15 and p16; very few cases or cell lines had p18 or p19 deletions or hypermethylation. Hyp...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2401043

    authors: Drexler HG

    更新日期:1998-06-01 00:00:00

  • New insight on the role of extrachromosomal retroviral DNA.

    abstract::During infection with different retroviruses, high levels of unintegrated extrachromosomal DNA accumulate in infected cells. While extrachromosomal linear DNA is the immediate precursor of the integrated provirus, the function, if any, of extrachromosomal circular DNA has been unclear. Several groups have attempted to...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2400776

    authors: Cara A,Reitz MS Jr

    更新日期:1997-09-01 00:00:00

  • Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group.

    abstract::Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with dif...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/leu.2012.336

    authors: Fernández de Larrea C,Kyle RA,Durie BG,Ludwig H,Usmani S,Vesole DH,Hajek R,San Miguel JF,Sezer O,Sonneveld P,Kumar SK,Mahindra A,Comenzo R,Palumbo A,Mazumber A,Anderson KC,Richardson PG,Badros AZ,Caers J,Cavo M,Le

    更新日期:2013-04-01 00:00:00

  • Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H.

    abstract::Chronic lymphocytic leukemia (CLL) cells could be undetectable by flow cytometry or polymerase chain reaction after sequential treatment with fludarabine and Campath-1H. Concern has been raised regarding the ability to mobilize sufficient peripheral blood progenitor cells (PBPCs) for autografting after purine analogue...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2403190

    authors: Montillo M,Tedeschi A,Rossi V,Cairoli R,Pungolino E,Intropido L,Cafro AM,D'Avanzo G,Farioli R,Brando B,Scarpati B,Veronese S,Morra E

    更新日期:2004-01-01 00:00:00

  • Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

    abstract::Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate ant...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2015.50

    authors: Wild J,Schmiedel BJ,Maurer A,Raab S,Prokop L,Stevanović S,Dörfel D,Schneider P,Salih HR

    更新日期:2015-08-01 00:00:00

  • Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation.

    abstract::Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful. These minimal residual disease techniques would allow a...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2402550

    authors: Pérez-Simón JA,Caballero D,Diez-Campelo M,Lopez-Pérez R,Mateos G,Cañizo C,Vazquez L,Vidriales B,Mateos MV,Gonzalez M,San Miguel JF

    更新日期:2002-08-01 00:00:00

  • Prognostic value of residual normal metaphases in acute myelogenous leukemia patients presenting with abnormal karyotype.

    abstract::Two hundred and forty-four untreated acute myelogenous leukemia (AML) patients with unfavorable karyotypes and 109 others with favorable aneuploid karyotypes were used to evaluate the prognostic significance of having both normal and abnormal metaphases (AN) vs only abnormal metaphases (AA) at AML presentation. The AA...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Ghaddar HM,Pierce S,Reed P,Estey EH

    更新日期:1995-05-01 00:00:00

  • Myeloid differentiation antigens identify leukemic cell subpopulations with different cell cycle characteristics.

    abstract::In order to assess the proliferative capacity of leukemic subpopulations and to know whether it can be related to the stage of maturation, the expression of two surface antigens identifying distinct steps of leukocyte differentiation (CD15 and CD34) was studied by flow cytometry in correlation with DNA content in 16 c...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Campos L,Ffrench M,Guyotat D

    更新日期:1990-01-01 00:00:00

  • NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951.

    abstract::Risk-adjusted treatment stratification in T-cell acute lymphoblastic leukemias (T-ALLs) is currently based only on early response to chemotherapy. We investigated the prognostic implication of hyperactivation of NOTCH pathway resulting from mutations of NOTCH1 or FBXW7 in children with T-ALL enrolled in EORTC-CLG tria...

    journal_title:Leukemia

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1038/leu.2010.205

    authors: Clappier E,Collette S,Grardel N,Girard S,Suarez L,Brunie G,Kaltenbach S,Yakouben K,Mazingue F,Robert A,Boutard P,Plantaz D,Rohrlich P,van Vlierberghe P,Preudhomme C,Otten J,Speleman F,Dastugue N,Suciu S,Benoit Y,B

    更新日期:2010-12-01 00:00:00

  • Reconstitution of functional human GM-CSF receptor in mouse NIH3T3 fibroblasts and BA/F3 proB cells.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high affinity human GM-CSF receptor (hGM-CSFR) in a proB cell line BA/F3 by cotransfecting alpha and beta chain cDNA clones and showed that the reconstituted recep...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Yokota T,Watanabe S,Mui AL,Muto A,Miyajima A,Arai K

    更新日期:1993-08-01 00:00:00

  • Characterization of the leukemogenic potential of distal cytoplasmic CSF3R truncation and missense mutations.

    abstract::An increasing number of variants of unknown significance are being identified in leukemia patients with the application of deep sequencing and these include CSF3R cytoplasmic mutations. Previous studies have demonstrated oncogenic potential of certain CSF3R truncation mutations prior to internalization motifs. However...

    journal_title:Leukemia

    pub_type: 杂志文章,多中心研究

    doi:10.1038/leu.2017.126

    authors: Zhang H,Reister Schultz A,Luty S,Rofelty A,Su Y,Means S,Bottomly D,Wilmot B,McWeeney SK,Tyner JW

    更新日期:2017-12-01 00:00:00

  • BCL2 mutations in diffuse large B-cell lymphoma.

    abstract::BCL2 is deregulated in diffuse large B-cell lymphoma (DLBCL) by the t(14;18) translocation, gene amplification and/or nuclear factor-κB signaling. RNA-seq data have recently shown that BCL2 is the most highly mutated gene in germinal center B-cell (GCB) DLBCL. We have sequenced BCL2 in 298 primary DLBCL biopsies, 131 ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2011.378

    authors: Schuetz JM,Johnson NA,Morin RD,Scott DW,Tan K,Ben-Nierah S,Boyle M,Slack GW,Marra MA,Connors JM,Brooks-Wilson AR,Gascoyne RD

    更新日期:2012-06-01 00:00:00

  • Identification of a leukemia-initiating stem cell in human mast cell leukemia.

    abstract::Mast cell leukemia (MCL) is a highly fatal malignancy characterized by devastating expansion of immature mast cells in various organs. Although considered a stem cell disease, little is known about MCL-propagating neoplastic stem cells. We here describe that leukemic stem cells (LSCs) in MCL reside within a CD34+/CD38...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/s41375-019-0460-6

    authors: Eisenwort G,Sadovnik I,Schwaab J,Jawhar M,Keller A,Stefanzl G,Berger D,Blatt K,Hoermann G,Bilban M,Willmann M,Winding C,Sperr WR,Arock M,Rülicke T,Reiter A,Valent P

    更新日期:2019-11-01 00:00:00

  • The molecular characterization and clinical management of multiple myeloma in the post-genome era.

    abstract::Cancer-causing mutations disrupt coordinated, precise programs of gene expression that govern cell growth and differentiation. Microarray-based gene-expression profiling (GEP) is a powerful tool to globally analyze these changes to study cancer biology and clinical behavior. Despite overwhelming genomic chaos in multi...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/leu.2009.160

    authors: Zhou Y,Barlogie B,Shaughnessy JD Jr

    更新日期:2009-11-01 00:00:00

  • All-trans retinoic acid potentiates the inhibitory effects of interferon alpha on chronic myeloid leukemia progenitors in vitro.

    abstract::All-trans retinoic acid (ATRA) has recently been shown to synergize with the inhibitory effect of interferon alpha (IFN alpha) on the growth of malignant cells isolated from solid tumors. We investigated whether ATRA could potentiate the inhibitory effects of IFN alpha on the proliferation of leukemic progenitors in c...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2400611

    authors: Mahon FX,Chahine H,Barbot C,Pigeonnier V,Jazwiec B,Reiffers J,Ripoche J

    更新日期:1997-05-01 00:00:00

  • Expression of mRNA for serglycin core protein and other platelet alpha granule proteins is increased in human erythroleukemia cells by phorbol myristate acetate.

    abstract::This study has determined the effects of phorbol-12-myristate-13-acetate (PMA) and dimethylsulfoxide (DMSO) on mRNA levels for the serglycin proteoglycan core protein in human erythroleukemia (HEL) cells. We have compared these changes to those for mRNA for other proteins which are known to be synthesized by HEL cells...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Schick BP,Thornton RD

    更新日期:1993-12-01 00:00:00

  • Differential abilities of the Raf family of protein kinases to abrogate cytokine dependency and prevent apoptosis in murine hematopoietic cells by a MEK1-dependent mechanism.

    abstract::In this study, the abilities of constitutive and conditional forms of the three Raf kinases to abrogate the cytokine dependency of FDC-P1 cells were examined. The constitutively active forms (delta) of all three Raf kinases were fused to the hormone-binding domain of the estrogen receptor (ER), rendering their activit...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401720

    authors: Hoyle PE,Moye PW,Steelman LS,Blalock WL,Franklin RA,Pearce M,Cherwinski H,Bosch E,McMahon M,McCubrey JA

    更新日期:2000-04-01 00:00:00

  • Rearrangement of the retinoic acid receptor gene in acute promyelocytic leukemia.

    abstract::The retinoic acid receptor-alpha (RAR-alpha) gene was previously localized to chromosome 17q21, a region close to the t(15;17) (q22;q21) abnormality in acute promyelocytic leukemia (APL). We used the RAR-alpha gene as a probe and found that eight of nine APL patient samples with t(15;17) (q22;q21) showed rearranged ba...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Chang KS,Trujillo JM,Ogura T,Castiglione CM,Kidd KK,Zhao SR,Freireich EJ,Stass SA

    更新日期:1991-03-01 00:00:00

  • Lack of evidence for abnormal autocrine or paracrine mechanisms underlying the uncontrolled proliferation of primitive chronic myeloid leukemia progenitor cells.

    abstract::Previous studies have revealed a consistent defect in the cycling behavior of primitive neoplastic progenitor cells in patients with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML). This is manifested both in vivo and in long-term cultures of CML cells as an increased rate of turnover amongst Ph1...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Otsuka T,Eaves CJ,Humphries RK,Hogge DE,Eaves AC

    更新日期:1991-10-01 00:00:00

  • Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment.

    abstract::The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the exp...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2403647

    authors: Pérez-Andrés M,Almeida J,Martín-Ayuso M,Moro MJ,Martín-Nuñez G,Galende J,Borrego D,Rodríguez MJ,Ortega F,Hernandez J,Moreno I,Domínguez M,Mateo G,San Miguel JF,Orfao A,Spanish Network on multiple myeloma (G03\/136).,Spani

    更新日期:2005-03-01 00:00:00

  • Natural killer-cell malignancies: diagnosis and treatment.

    abstract::Natural killer (NK)-cell malignancies are uncommon diseases. Previously known as polymorphic reticulosis or angiocentric T-cell lymphomas, they are classified by the World Health Organization as NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia. They are prevalent in Asia and South America, but exceptiona...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2403955

    authors: Kwong YL

    更新日期:2005-12-01 00:00:00

  • Identification of circulating CD10 positive T cells in angioimmunoblastic T-cell lymphoma.

    abstract::In most cases of lymphomas with blood dissemination, the careful cytological analysis of peripheral blood smears provides a rapid orientation to diagnosis, even if the final subtyping is achieved by histology and eventually other techniques. Here, we evaluated if the analysis of blood smears may suggest the blood diss...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2404013

    authors: Baseggio L,Berger F,Morel D,Delfau-Larue MH,Goedert G,Salles G,Magaud JP,Felman P

    更新日期:2006-02-01 00:00:00

  • Suppression of c-myc and c-myb expression in myeloid cell lines treated with recombinant tumor necrosis factor-alpha.

    abstract::Proto-oncogenes are thought to be involved in cellular differentiation and proliferation. Tumor necrosis factors (TNFs) are specific cytokines that have cytostatic and cytotoxic effects in vitro against a wide range of human tumor cells. We have previously demonstrated that recombinant TNFs (rTNFs) have an antiprolife...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Schachner J,Blick M,Freireich E,Gutterman J,Beran M

    更新日期:1988-11-01 00:00:00

  • Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia.

    abstract::Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT an...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2015.98

    authors: Ruggeri A,Labopin M,Sanz G,Piemontese S,Arcese W,Bacigalupo A,Blaise D,Bosi A,Huang H,Karakasis D,Koc Y,Michallet M,Picardi A,Sanz J,Santarone S,Sengelov H,Sierra J,Vincent L,Volt F,Nagler A,Gluckman E,Ciceri F

    更新日期:2015-09-01 00:00:00

  • MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML.

    abstract::Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to potently induce apoptosis in various malignant cells by inhibiting RNA synthesis and nuclear factor-κB activity. Previously, we showed that triptolide promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria-mediated path...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2011.246

    authors: Carter BZ,Mak DH,Shi Y,Fidler JM,Chen R,Ling X,Plunkett W,Andreeff M

    更新日期:2012-03-01 00:00:00

  • Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells.

    abstract::CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assa...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2404312

    authors: Kimura H,Morii E,Ikeda JI,Ezoe S,Xu JX,Nakamichi N,Tomita Y,Shibayama H,Kanakura Y,Aozasa K

    更新日期:2006-09-01 00:00:00