Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma.

Abstract:

:This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m2 days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort. Patients received a median of 2 prior lines of therapy; 97% bortezomib exposed. With no dose-limiting toxicities, MTD was defined as the maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2 and LoDEX. All patients discontinued treatment by data cutoff (2 April 2015). The most common grade 3/4 treatment-emergent adverse events were neutropenia (44%) and thrombocytopenia (26%), which occurred more frequently with IV than SC bortezomib. No grade 3/4 peripheral neuropathy or deep vein thrombosis was reported. Overall response rate was 65%. Median duration of response was 7.4 months. Pomalidomide, bortezomib and LoDEX was well tolerated and effective in lenalidomide-refractory and bortezomib-exposed patients with RRMM.

journal_name

Leukemia

journal_title

Leukemia

authors

Richardson PG,Hofmeister CC,Raje NS,Siegel DS,Lonial S,Laubach J,Efebera YA,Vesole DH,Nooka AK,Rosenblatt J,Doss D,Zaki MH,Bensmaine A,Herring J,Li Y,Watkins L,Chen MS,Anderson KC

doi

10.1038/leu.2017.173

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

2695-2701

issue

12

eissn

0887-6924

issn

1476-5551

pii

leu2017173

journal_volume

31

pub_type

杂志文章

相关文献

LEUKEMIA文献大全
  • Ethnic and geographic diversity of chronic lymphocytic leukaemia.

    abstract::East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations ar...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/s41375-020-01057-5

    authors: Yang S,Varghese AM,Sood N,Chiattone C,Akinola NO,Huang X,Gale RP

    更新日期:2020-10-19 00:00:00

  • High-affinity FRβ-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity.

    abstract::Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) f...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2016.35

    authors: Lynn RC,Feng Y,Schutsky K,Poussin M,Kalota A,Dimitrov DS,Powell DJ Jr

    更新日期:2016-06-01 00:00:00

  • Deletion of chromosome 2 is an early event in the development of radiation-induced myeloid leukemia in SJL/J mice.

    abstract::In this study we have analyzed the chromosomal changes in the preleukemic phase in SJL/J mice treated with radiation and acute myeloid leukemias (AMLs) induced by radiation alone or with additional corticosteroid treatment. SJL/J mice exposed to 300 rad whole body irradiation developed a low incidence of AML (20-25%) ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Trakhtenbrot L,Krauthgamer R,Resnitzky P,Haran-Ghera N

    更新日期:1988-08-01 00:00:00

  • Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV.

    abstract::Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecul...

    journal_title:Leukemia

    pub_type: 杂志文章,随机对照试验

    doi:10.1038/s41375-018-0055-7

    authors: Saussele S,Hehlmann R,Fabarius A,Jeromin S,Proetel U,Rinaldetti S,Kohlbrenner K,Einsele H,Falge C,Kanz L,Neubauer A,Kneba M,Stegelmann F,Pfreundschuh M,Waller CF,Oppliger Leibundgut E,Heim D,Krause SW,Hofmann WK,Has

    更新日期:2018-05-01 00:00:00

  • Mast cell growth factor, a ligand for the receptor encoded by c-kit, affects the growth in culture of the blast cells of acute myeloblastic leukemia.

    abstract::The c-kit proto-oncogene encodes a transmembrane receptor with a tyrosine kinase internal domain. C-kit has been mapped to the W locus in the mouse, and the gene encoding the ligand has been shown to be the product of the murine SI locus. Previous genetic studies have shown that the murine W and SI loci play important...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Wang C,Koistinen P,Yang GS,Williams DE,Lyman SD,Minden MD,McCulloch EA

    更新日期:1991-06-01 00:00:00

  • Kinetics of chimerism during the early post-transplant period in pediatric patients with malignant and non-malignant hematologic disorders: implications for timely detection of engraftment, graft failure and rejection.

    abstract::The monitoring of chimerism by PCR has become a routine diagnostic approach in patients after allogeneic bone marrow or peripheral blood stem cell transplantation. Nevertheless, a temporal correlation between molecular and hematologic assessment of engraftment has not been clearly established. To address this issue, a...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Dubovsky J,Daxberger H,Fritsch G,Printz D,Peters C,Matthes S,Gadner H,Lion T,Muller-Bérat N

    更新日期:1999-12-01 00:00:00

  • An atlas of bloodstream-accessible bone marrow proteins for site-directed therapy of acute myeloid leukemia.

    abstract::The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tu...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2017.208

    authors: Angenendt L,Reuter S,Kentrup D,Benk AS,Neumann F,Hüve J,Martens AC,Schwöppe C,Kessler T,Schmidt LH,Sauer T,Brand C,Mikesch JH,Lenz G,Mesters RM,Müller-Tidow C,Hartmann W,Wardelmann E,Neri D,Berdel WE,Roesli C,Sc

    更新日期:2018-02-01 00:00:00

  • Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells.

    abstract::Lovastatin is an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the major regulatory enzyme of the mevalonate pathway. We have previously reported that lovastatin induces a significant apoptotic response in human acute myeloid leukemia (AML) cells. To identify the critical biochemic...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2402196

    authors: Xia Z,Tan MM,Wong WW,Dimitroulakos J,Minden MD,Penn LZ

    更新日期:2001-09-01 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

  • Pulmonary leukostasis secondary to all-trans retinoic acid in the treatment of acute promyelocytic leukemia in first relapse.

    abstract::All-trans retinoic acid has recently been shown to induce differentiation of acute promyelocytic leukemia cells in vitro and in vivo. Clinical trials of patients treated de novo, in first relapse, and with resistant disease have achieved a high rate of complete remission (CR). The overall toxicity is substantially les...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Vosburgh E

    更新日期:1992-06-01 00:00:00

  • Long-term results following treatment of newly-diagnosed acute myelogenous leukemia with continuous-infusion high-dose cytosine arabinoside.

    abstract::The long-term results in 130 patients with newly diagnosed acute myelogenous leukemia treated with continuous infusion high-dose ara-C (1.5 gm/m2/day x 4 days, CIHDAC) were compared with those in 264 patients treated in previous studies with standard dose ara-C (70-90 mg/m2/d x 7 days) plus either adriamycin (Ad-OAP),...

    journal_title:Leukemia

    pub_type: 临床试验,杂志文章

    doi:

    authors: Ghaddar HM,Plunkett W,Kantarjian HM,Pierce S,Freireich EJ,Keating MJ,Estey EH

    更新日期:1994-08-01 00:00:00

  • Induction treatment of acute promyelocytic leukemia using all-trans retinoic acid. Controversies about dosage, advantages and side-effect management.

    abstract::All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) represents the leading example of targetted drugs for inducing an in vivo differentiation of malignancy (1,2). A fixed dose of 45 mg/m2/day was proposed for the treatment of patients (3), according to the results obtained by retinoic acid derivatives...

    journal_title:Leukemia

    pub_type: 临床试验,杂志文章

    doi:

    authors: Dombret H,Castaigne S,Fenaux P,Chomienne C,Degos L

    更新日期:1994-01-01 00:00:00

  • Human myeloma cells express the bone regulating gene Runx2/Cbfa1 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients.

    abstract::Osteopontin (OPN) is a multifunctional bone matrix glycoprotein that is involved in angiogenesis, cell survival and tumor progression. In this study we show that human myeloma cells directly produce OPN and express its major regulating gene Runx2/Cbfa1. The activity of Runx2/Cbfa1 protein in human myeloma cells has al...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2403976

    authors: Colla S,Morandi F,Lazzaretti M,Rizzato R,Lunghi P,Bonomini S,Mancini C,Pedrazzoni M,Crugnola M,Rizzoli V,Giuliani N

    更新日期:2005-12-01 00:00:00

  • A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes.

    abstract::The use of darbepoetin alfa to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS) was evaluated in a phase 3 trial. Eligible patients had low/intermediate-1 risk MDS, hemoglobin ⩽10 g/dl, low transfusion burden and serum erythropoietin (EPO) ⩽500 mU/ml. Patients were randomized 2:1 to receive 24 ...

    journal_title:Leukemia

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1038/leu.2017.192

    authors: Platzbecker U,Symeonidis A,Oliva EN,Goede JS,Delforge M,Mayer J,Slama B,Badre S,Gasal E,Mehta B,Franklin J

    更新日期:2017-09-01 00:00:00

  • Structure of Bcl-1 and IgH-CDR3 rearrangements as clonal markers in mantle cell lymphomas.

    abstract::Mantle cell lymphoma represent a clinicopathologically distinct entity of malignant non-Hodgkin's lymphoma (NHL) and are characterized by a specific chromosomal translocation t(11;14)(q13;q32) involving the cyclin D1 gene also designated as bcl-1/PRAD1 gene on chromosome 11 and the heavy chain immunoglobulin joining r...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401172

    authors: Pott C,Tiemann M,Linke B,Ott MM,von Hofen M,Bolz I,Hiddemann W,Parwaresch R,Kneba M

    更新日期:1998-10-01 00:00:00

  • Does chemotherapy modify the immune surveillance of hematological malignancies?

    abstract::Malignant diseases induce immune responses against them which have variable success in controlling progression of disease. A variety of congenital and acquired disorders provide evidence in support of T cell or NK cell immune surveillance mechanisms in human hematological malignancies. Furthermore, clinical experience...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/leu.2008.273

    authors: Barrett AJ,Savani BN

    更新日期:2009-01-01 00:00:00

  • SIV/HIV-1 chimeric viruses having HIV-1 env gene: a new animal model and a candidate for attenuated live vaccine.

    abstract::In order to generate an HIV-1, which is infectious to and induces AIDS-like disease in monkeys, an SIVmac/HIV-1 chimeric virus, designated NM-3rN, which was replication-competent in monkeys, was constructed by recombination between HIV-1 and SIV mac genomes. The NM-3rN enabled to evaluate the efficacy of HIV-1 Env-dir...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Hayami M,Igarashi T

    更新日期:1997-04-01 00:00:00

  • Triazene compounds induce apoptosis in O6-alkylguanine-DNA alkyltransferase deficient leukemia cell lines.

    abstract::Previous studies demonstrated that triazene compounds (TZC) possess antitumor, antimetastatic and immunosuppressive activity, and induce novel antigenic properties in neoplastic cells. Moreover, TZC showed marked antitumor activity in patients with acute myelogenous leukemias (AML). In most cases leukemic blasts with ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Tentori L,Graziani G,Gilberti S,Lacal PM,Bonmassar E,D'Atri S

    更新日期:1995-11-01 00:00:00

  • Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease.

    abstract::We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outco...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Göker E,Lin JT,Trippett T,Elisseyeff Y,Tong WP,Niedzwiecki D,Tan C,Steinherz P,Schweitzer BI,Bertino JR

    更新日期:1993-07-01 00:00:00

  • Trial of IFN or STI571 before proceeding to allografting for CML?

    abstract::Ten-year survival of IFN-treated low risk CML patients is about 40%, and more in cytogenetic responders. Allografting has a cure rate of up to 75%, but is associated with considerable procedure related morbidity and mortality. One out of three or four is likely not to survive. A comparative quantification of survival ...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2401874

    authors: Hehlmann R

    更新日期:2000-09-01 00:00:00

  • VEGF receptors on chronic lymphocytic leukemia (CLL) B cells interact with STAT 1 and 3: implication for apoptosis resistance.

    abstract::We have previously shown that chronic lymphocytic leukemia (CLL) B cells secrete vascular endothelial growth factor (VEGF) in vitro, have constitutively active VEGF receptors R1 and R2, and respond to exogenous VEGF by specifically upregulating Mcl-1 and XIAP in association with decreased cell death. We found that epi...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2403667

    authors: Lee YK,Shanafelt TD,Bone ND,Strege AK,Jelinek DF,Kay NE

    更新日期:2005-04-01 00:00:00

  • IL-6 trans-signaling promotes the expansion and anti-tumor activity of CAR T cells.

    abstract::Chimeric antigen receptor (CAR) T cell therapies lead to high clinical response rates in B cell malignancies, and are under investigation for treatment of solid tumors. While high systemic interleukin- (IL-) 6 levels are associated with clinical cytokine release syndrome (CRS), the role of IL-6 trans-signaling within ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/s41375-020-01085-1

    authors: Jiang Z,Liao R,Lv J,Li S,Zheng D,Qin L,Wu D,Chen S,Long Y,Wu Q,Wang S,Lin S,Huang X,Tang Z,Shi P,Zhou H,Liu Q,Zhao R,Li Y,Jie Y,Wei W,Lai P,Du X,Cui S,Weinkove R,Liu P,Pei D,Yao Y,Li P

    更新日期:2020-11-09 00:00:00

  • A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia.

    abstract::The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56-84) and norm...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2016.225

    authors: Burnett AK,Russell NH,Hills RK,Kell J,Nielsen OJ,Dennis M,Cahalin P,Pocock C,Ali S,Burns S,Freeman S,Milligan D,Clark RE

    更新日期:2017-02-01 00:00:00

  • Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis in pediatric bone marrow.

    abstract::We studied the differentiation profiles of B cell precursors (BCP) in normal and post-chemotherapy pediatric bone marrow (BM) using multiparameter flow cytometry. The goal of our study was to draw a comprehensive phenotypic map of the three major maturational BCP stages in BM. By correlating lineage-associated markers...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2400732

    authors: Dworzak MN,Fritsch G,Fleischer C,Printz D,Fröschl G,Buchinger P,Mann G,Gadner H

    更新日期:1997-08-01 00:00:00

  • Potential antileukemic effect of gamma delta T cells in acute lymphoblastic leukemia.

    abstract::The immune response to leukemia is poorly understood. We postulated that nonmalignant T lymphocytes remaining within bone marrow from children with newly diagnosed ALL could be involved in this immune response. T lymphocytes which expressed gamma delta TCR comprised less than 1% of ALL marrow cells. A preferential out...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Duval M,Yotnda P,Bensussan A,Oudhiri N,Guidal C,Rohrlich P,Boumsell L,Grandchamp B,Vilmer E

    更新日期:1995-05-01 00:00:00

  • Lack of CD95/FAS gene somatic mutations in extranodal, nodal and splenic marginal zone B cell lymphomas.

    abstract::Germline CD95 (also known as FAS, APT1 and APO1) gene mutations have been associated with benign lymphoproliferative diseases and autoimmune processes. Somatic mutations have been reported in human tumours, including lymphomas. Since marginal zone B cell lymphomas usually arise in a background of chronic inflammation,...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401708

    authors: Bertoni F,Conconi A,Luminari S,Realini C,Roggero E,Baldini L,Carobbio S,Cavalli F,Neri A,Zucca E

    更新日期:2000-03-01 00:00:00

  • Microsatellite instability in childhood T cell acute lymphoblastic leukemia.

    abstract::Acute lymphoblastic leukemia (ALL) is the most frequent cancer encountered in children. Little is known about the molecular pathology of childhood T cell ALL. Oncogenesis is a multistep process that involves alterations in proto-oncogenes and tumor suppressor genes. Recently, a mutator phenotype detectable by microsat...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2400650

    authors: Baccichet A,Benachenhou N,Couture F,Leclerc JM,Sinnett D

    更新日期:1997-06-01 00:00:00

  • Reconstitution of peripheral blood lymphocyte subsets in the long-term disease-free survivors of patients with acute myeloblastic leukemia.

    abstract::The number of long-term survivors of patients with acute myeloblastic leukemia (AML) has increased as a result of the progress of chemotherapy. We examined the recovery of peripheral blood lymphocytes (PBL) subset after chemotherapy to clarify the reconstitution of the immune system in AML. Thirty patients with AML in...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2400891

    authors: Ohnishi K,Yamanishi H,Naito K,Utsumi M,Yokomaku S,Hirabayashi N,Ohno R

    更新日期:1998-01-01 00:00:00

  • FHL2 regulates hematopoietic stem cell functions under stress conditions.

    abstract::FHL2, a member of the four and one half LIM domain protein family, is a critical transcriptional modulator. Here, we identify FHL2 as a critical regulator of hematopoietic stem cells (HSCs) that is essential for maintaining HSC self-renewal under regenerative stress. We find that Fhl2 loss has limited effects on hemat...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2014.254

    authors: Hou Y,Wang X,Li L,Fan R,Chen J,Zhu T,Li W,Jiang Y,Mittal N,Wu W,Peace D,Qian Z

    更新日期:2015-03-01 00:00:00

  • RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation.

    abstract::Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. A...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/s41375-019-0403-2

    authors: Zhou N,Gutierrez-Uzquiza A,Zheng XY,Chang R,Vogl DT,Garfall AL,Bernabei L,Saraf A,Florens L,Washburn MP,Illendula A,Bushweller JH,Busino L

    更新日期:2019-08-01 00:00:00