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  • 1
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    Clinical observations of AML expressing mutant RUNX1 and pre-clinical studies of RUNX1-targeted novel therapy of AML.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 7030-7030
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 7030-7030
    Abstract: 7030 Background: Runt-related transcription factor 1 ( RUNX1) is critically involved in normal and malignant hematopoiesis. Somatic mutations in RUNX1 occur in ~10% of AML, especially in older patients with history of radiation or antecedent hematologic disorder. Presence of mRUNX1 is reported to confer relative resistance to therapy and poorer prognosis in AML, and there are no mRUNX1-targeted or specific therapies available. Methods: We retrospectively analyzed outcomes of 94 mRUNX1 and 444 wild-type RUNX1 AML patients treated at our institution from 9/2013 to 12/2016. We also determined the pre-clinical efficacy of a targeted therapy against cultured and primary AML cells expressing mRUNX1. Results: 67% of mRUNX1 patients were 〉 65 years of age. Co-occurring mutations with mRUNX1 were ASXL1 (33%), N/KRAS (20%), FLT3 (20%), IDH2 (18%), IDH1 (13%) and TET2 (10%). In patients 〉 65 years treated with hypomethylating agent-based therapy, the presence or absence of mRUNX1 did not impact response rate (42% vs 46% CR/CRp, p = 0.67), median event-free survival (3.4 vs 4.7 mo, p = 0.82) or overall survival (11.5 vs 9.3 mo, p = 0.97). In mRUNX1 expressing AML OCI-AML5 and MonoMac1 cells, knockdown of RUNX1 by shRNA repressed its targets, e.g., MYC and PU.1, inhibited growth and induced apoptosis. Ex vivo knockdown of RUNX1 abrogated in vivo leukemia initiation by OCI-AML5 cells. After engraftment, inducible shRNA-mediated in vivo knockdown of RUNX1 restored survival of immune-depleted NSG mice engrafted with OCI-AML5 cells. RUNX1 transcription is driven by a super enhancer occupied by the bromodomain extraterminal protein (BETP), BRD4. Accordingly, BRD4 knockdown by shRNA or treatment with the BRD4-inhibitor OTX015 depleted RUNX1 and its targets, and induced apoptosis of AML cells. Treatment of OCI-AML5 cell-engrafted NSG mice with OTX015 (50 mg/Kg/day X 5, for 3 wks) reduced AML burden and improved survival (p 〈 0.01). Co-treatment with the BETi and BCL2 inhibitor venetoclax or CDK4/6 antagonist palbociclib or decitabine synergistically induced apoptosis of OCI-AML5 and primary AML blasts. Conclusions: These findings highlight a novel, promising, BETP antagonist-based therapy of AML expressing mtRUNX1.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.7030
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Patterns of leukemic transformation in patients with TP53 -mutant myelodysplastic syndromes.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 7054-7054
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 7054-7054
    Abstract: 7054 Background: TP53 is the most frequently mutated gene in human cancers, including 7-13% of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. Although it is associated with transformation to AML in patients with MDS, the additional genomic events leading to transformation are poorly understood. Methods: We retrospectively evaluated 312 patients with TP53-mutated AML or MDS diagnosed between 2013-2016. Patient characteristics and bone marrow data, including cytogenetic and next generation sequencing information, were assessed at the time of diagnosis and progression to AML. Results: There were 151 TP53-mutated MDS patients and 161 TP53-mutated de novo AML patients with a median follow-up time of 34.1 months. Forty-one patients with TP53-mutated MDS transformed to AML. Sequencing data at transformation was available in 17 patients (41%). At diagnosis, median age was 67 with 2 patients with intermediate-risk, 7 patients with high-risk, and 32 patients with very high-risk MDS by IPSS-R. Complex karyotype was seen in 40 patients, and 12 patients had 1, 25 patients had 2, and 4 patients had 3 TP53 abnormalities. Predictors of transformation to AML include TP53 loss of heterozygosity (p = 0.008), 3 TP53 abnormalities (p = 0.049), complex cytogenetics (p = 0.023), and female gender (p = 0.002). Median time to transformation was 10.4 months. At transformation, an increase in TP53 variant allelic frequency was observed in 7 patients (41%), and new mutations, particularly NRAS, IDH1, TP53, MLL, KDM6A, TET2, and NOTCH1, were acquired by 10 patients (59%). Cytogenetic evaluation revealed identical clones in 5 patients, linear acquisition of cytogenetic abnormalities in 12 patients, and new clones in 8 patients. Patients with TP53-mutated AML from MDS also had worse median overall survival than patients with TP53-mutated de novo AML at 2.5 months vs. 5.7 months respectively (p 〈 0.001). Conclusions: TP53 mutations confer a worse prognosis, especially in the setting of AML transformed from MDS. This may be due to the acquisition of new mutations and cytogenetic abnormalities. Further exploration of the biological mechanisms leading to transformation in TP53-mutant MDS is warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.7054
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
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    AML patients with IDH1 or IDH2 mutations treated with hypomethylating agents: A case series.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 6576-6576
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 6576-6576
    Abstract: 6576 Background: Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations play a significant role in acute myeloid leukemia (AML), yet optimal treatment for AML patients with IDH mutations remains unclear. IDH mutations have been associated with a globally hypermethylated genomic state, as the result of increased levels of 2-HG, a regulator of histone methylation. We sought to retrospectively determine responses of patients with IDH-mutated AML to treatment with hypomethylating agents. Methods: We reviewed clinical data for AML patients treated at The University of Texas M. D. Anderson Cancer Center from June 2001 to December 2011 whose stored leukemia samples from bone marrow aspirateshad been tested retrospectively for IDH1 and IDH2 mutations. We searched three databases that contained records for 407 AML patients. We selected patients who had been treated with the hypomethylating agents 5-azacitidine or decitabine, alone or in conjunction with other therapeutics. We retrospectively reviewed the patients’ medical records to obtain demographic, laboratory, treatment, and clinical data. We evaluated response measured by remission status, reduction in bone marrow blasts and peripheral blood blasts, and time to relapse. Results: We identified 104 patients (25.6%) who had either an IDH1 or IDH2 mutation, and of these, 8 patients had also been treated with hypomethylating agents. A ninth AML patient, who is IDH2-mutant, is currently undergoing treatment with decitabine alone. Of these 9 patients, three had a durable complete remission without recovery of blood counts (CRp), three had a partial response (PR), with or without blood count recovery, and three had no response. All 9 patients did have an initial decrease in the percentage of bone marrow blasts, peripheral blood blasts, or both. Conclusions: This series of patients demonstrates the possibility that AML patients with IDH1 or IDH2 mutations benefit from the use of hypomethylating agents, and suggests it is worthwhile to prospectively investigate treatment of patients with IDH-mutated AML using hypomethylating agents.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.6576
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Immune-related gene expression deficit of leukemia stem cells (LSC) in AML.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 7011-7011
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 7011-7011
    Abstract: 7011 Background: AML LSC are believed to be responsible for residual and resistant leukemic disease leading to relapse. Understanding differences between bulk AML and the LSC subpopulation may allow the identification of novel LSC targets, especially for the most adverse risk AML where few patients are cured. Targeting LSC may be needed to eradicate AML, and immune-based therapies provide an approach for eliminating LSC. The transcriptional landscape of immune-related genes in LSC is not well understood. Methods: Samples were collected at diagnosis from 12 patients with high-risk AML prior to therapy. Bulk (CD45-dim blasts) and LSC (Lin-CD34+CD38-CD123+) AML marrow cells were FACS-sorted and analyzed using whole genome RNA-sequencing. Transcriptomes were analyzed using AltAnalyze software to identify differentially expressed genes in bulk AML cells and in AML LSC populations. These genes were further assessed by gene enrichment analysis using data from Gene Ontology (GO) and the Cancer Genome Atlas Project (CGAP). Results: Sixty-eight genes were identified with greater than 3-fold differential expression between bulk AML and LSC. GO enrichment analysis demonstrated more than 10-fold enrichment of genes involved in the molecular functions, biologic processes, and cell components related to the antigen presentation pathway, with the comparative down-regulation occurring in LSC. Among the top differentially expressed gene clusters, both the MHC class II and interferon-gamma signaling/response pathway gene expression was blunted in LSC. Additional expression analysis revealed that 42% of a CGAP-curated list of 201 antigen-processing and -presentation genes had significantly decreased expression in the LSC subpopulation compared to bulk AML. Conclusions: LSC from primary AML patient samples are characterized by reduction in expression of MHC class II receptor and antigen presentation genes compared to bulk AML. These results suggest that impairment in the presentation and/or processing of tumor associated antigens by MHC class II on LSC, along with tonic sponging of immune response cells and diversion away from LSC by bulk AML, may contribute to LSC evasion of immune surveillance and response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.7011
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Characterization of Philadelphia-negative myeloproliferative neoplasm patients with chromosome 12 abnormalities.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 7112-7112
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 7112-7112
    Abstract: 7112 Background: Chromosome 12 (Chr 12) abnormalities have been reported as infrequent events in myelofibrosis (MF). Structural abnormalities at 12q13-15 and 12q24 have been reported in primary MF (PMF), and understanding genes at these loci, such as Hmga2 and Lnk may help in the treatment of Philadelphia-negative (Ph-neg) myeloproliferative neoplasms (MPN). We sought to better characterize Ph-neg MPN patients (pts) with Chr 12 aberrations. Methods: We queried a database of pts with any Ph-neg MPN who were referred to MD Anderson Cancer Center from 1985 to 2012. We identified pts with Chr 12 abnormalities and reviewed available clinical information. We compared characteristics and outcomes of pts who had Chr 12 abnormalities with pts who had no Chr 12 abnormality. Results: Of 1,787 pts with Ph-neg MPN, 36 pts (2%) were found to have a Chr 12 abnormality. Of these, 31 (86%) had MF, 1 (3%) had polycythemia vera (PV), 3 (8%) had hypereosinophilic syndrome, and 1 (3%) had unspecified MPN. Fourteen pts (39%) had successive biopsies demonstrating evolving cytogenetic abnormalities. The percentage of pts with MF was significantly higher among patients with Chr 12 abnormalities (86% vs. 54%, p-value 〈 0.001). A larger fraction of MF pts with Chr 12 abnormalities had post-PV MF (PPMF) (31% vs. 14%, p-value 〈 0.001). Age, JAK2 status, and incidence and rate of leukemic transformation from MF were not significantly different between the two groups. Of the 31 Chr 12 pts with MF, 12 (39%) had an abnormality at 12q13, 8 (26%) at 12q24, 6 (19%) had trisomy 12, 5 (16%) at 12q15, and 6 (19%) had another Chr 12 abnormality. Four pts (13%) had a structural abnormality at 〉 1 site along the long arm of Chr 12. Survival of Chr 12 MF pts as a whole or subdivided by chromosomal abnormality was not significantly different than MF pts without Chr 12 abnormalities. Conclusions: Our investigation into pts with Ph-neg MPN harboring Chr 12 abnormalities is the largest of its kind, and shows 3% of MF pts possessed some type of Chr 12 abnormality, most frequently at 12q13. We found that Chr 12 Ph-neg MPN pts were more likely to have MF and PPMF. Further investigation into the functional significance of these structural abnormalities is warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.7112
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Frequency and type of JAK3 variants in adult patients with leukemia.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e13117-e13117
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e13117-e13117
    Abstract: e13117 Background: Janus kinases (JAK) family members ( JAK1, JAK2, JAK3, TYK2) are involved in tumorigenesis. JAK3 activating variants, including V722I, demonstrably induce cellular transformation in vitro. The prevalence of JAK3 variants/mutations in leukemia, particularly in AML, and their role in leukemogenesis, remains unclear Methods: We retrospectively reviewed leukemia patients (pts) treated at MD Anderson Cancer Center between 2012 and 2016, whose marrow samples were tested for JAK3 variants/mutations by next generation sequencing. We evaluated the type and prevalence of variants, the demographics, laboratory, treatment, and clinical information for JAK3 pts. Results: A total of 28 leukemia pts with JAK3 variants were identified, and included: MDS/MPN (n = 4), CLL (n = 2) and B-cell ALL (n = 1). All 7 non-AML pts had V722I variant (in the pseudokinase domain). Twenty-one AML pts were identified; this included 15 pts with V722I (1.5%) out of total 977 AML pts tested, demonstrating this variant was significantly more prevalent in AML pts than in the general population (1.5 vs 0.9%, P= 0.04). Three pts (0.3%) had P151R (FERM domain), and 1 pt each (0.1%) had V718L (pseudokinase), R925L (kinase), and L940V (kinase), none of which have been previously described. A pt with T815M (between pseudokinase-kinase domains) was identified from outside genetic testing. For AML pts, median allelic frequency for variants was 52% (range, 41-88) and median marrow blasts was 42% (range 21-97); 10% of AML patients had complex karyotype. Concomitant mutations were most commonly found in IDH1/2 (n = 10), TP53 (n = 8), FLT3 (n = 5), NPM1 (n = 5), ASXL1 (n = 5), RUNX1 (n = 4), DNMT3A (3), and TET2 (n = 3). Conclusions: We report the largest survey of JAK3 variants among adult leukemia pts, with detailed and novel variants described for AML. Given allelic frequencies, JAK3 variants may represent germline polymorphisms in most cases; however the activating V722I variant has increased prevalence among AML pts. The existence of an FDA-approved JAK3 inhibitor tofacitinib, and the prevalence and location of JAK3 variants provide a basis for additional investigations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e13117
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Effect of vorinostat use on survival in patients with acute myeloid leukemia (AML) with FLT3 ITD mutations.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e18019-e18019
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e18019-e18019
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e18019
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Prognostic significance of early dynamics of peripheral blood counts in patients with AML/MDS undergoing induction chemotherapy.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e18045-e18045
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e18045-e18045
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e18045
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Venetoclax (VEN) and tyrosine kinase inhibitor (TKI) combinations in Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) and chronic myeloid leukemia myeloid blast phase (CML MBP).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e18515-e18515
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e18515-e18515
    Abstract: e18515 Background: Ph+ AML and CML MBP have poor outcomes. VEN synergizes with BCR-ABL TKIs in vitro and may eradicate Ph+ leukemic stem cells. However, the clinical activity of VEN+TKI regimens is unknown. Methods: We conducted a retrospective study on patients (pts) with Ph+ AML and CML MBP who received regimens with VEN+TKI at our institution. Results: We identified 6 pts with relapsed/refractory (R/R) Ph+ AML and 7 with CML MBP (2 transformed from chronic phase, 5 R/R). 10 pts (77%) were refractory to prior therapy and 3 (23%) had relapsed disease. Pt characteristics are shown in the Table. 5 AML pts (83%) had complex cytogenetics. Pts with CML MBP had received a median of 2 prior TKIs (range 1-3). 7 pts received decitabine-based combinations and 6 pts received intensive chemotherapy in combination with VEN+TKI. TKIs included ponatinib (n=7), dasatinib (n=4), bosutinib (n=1) and nilotinib (n=1). Among 12 evaluable pts, the overall response rate (CR + CRi + MLFS) was 50% (Table). In addition, 1 pt with AML developed aplastic marrow, underwent stem cell transplantation, and is still alive. Pts with CR/CRi vs. those without CR/CRi had higher median number of Ph+ metaphases (100% vs. 32%, p 〈 0.01) and higher baseline BCR-ABL1 PCR (100% vs. 0.5% p=0.01). The only AML pt who achieved CR/CRi had 100% Ph+ metaphases. After a median follow-up of 10.9 months (mo), 5 pts are alive (1 AML, 4 CML MBP). The median overall survival for pts with AML and CML MBP were 2 mo and not reached, respectively. The median relapse-free survival was 8.2 mo. Conclusions: VEN+TKI combinations show encouraging activity in pre-treated, advanced Ph+ leukemias, particularly CML MBP. Clonal burden of Ph+ cells correlated with response. Prospective trials are needed to evaluate VEN+TKI combinations in Ph+ leukemias. Pt characteristics and outcomes (n/N [%] / median [range]). [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e18515
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Phase I study of lurbinectedin (PM11083) in patients with advanced AML and MDS.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e18521-e18521
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e18521-e18521
    Abstract: e18521 Background: The FDA-approved drug trabectedin is a DNA minor groove binder (MGB) with activity against translocation-associated sarcomas. Lurbinectedin is a next-generation MGB, with activity against myeloid leukemia cells. A phase I clinical trial was initiated to determine recommended doses in MDS/AML. Further assessment of its safety, tolerability, and pharmacogenetics were studied. Methods: In total, 42 patients with relapsed/refractory MDS/AML received lurbinectedin, using a 3+3 study design. It was administered as a 1-hour IV infusion first at 3.5, 5, 6, and 7mg per dose on days 1 and 8. Subsequently, it was administered on days 1, 2, and 3, using 1, 1.5, 2, or 3mg per dose per patient. Results: Three patients had dose-limiting toxicities (DLTs), which were rhabdomyolysis (up to gr 4), hyperbilirubinemia (gr 3), and oral herpes (gr 3). All DLTs occurred in the 6 and 7mg cohorts. Adverse events included febrile neutropenia/infections (n = 3), GI (n = 6) and pulmonary (n = 2) toxicity, hyperhidrosis (n = 1), and QT prolongation (n = 1). Overall, 33 of 42 patients (79%) had reduction of blasts in peripheral blood (PB) or bone marrow (BM) at nadir, including 23 (55%) with 〉 50% reduction in PB blasts alone (n = 18) or both BM and PB blasts (n = 5). One patient had PR, 2 patients had morphologic leukemia-free survival, and most (n = 30) were discontinued for progressive disease. Early deaths occurred from disease-related causes, not attributable to lurbinectedin. Thirty-two patients treated at MD Anderson were analyzed for clinical characteristics and responses. Notably, among patients with follow-up bone marrow biopsy, those with a cytogenetic abnormality at chromosome 11q21-23 had significantly greater bone marrow blast reduction than those without such abnormality (change in percentage blasts: -31±14% [n = 4] vs. 8±8% [n = 16] , respectively; P= 0.04). Conclusions: Lurbinectedin is generally safe and tolerated at dose levels tested. While no sustained remissions 〉 3 cycles were observed in these highest-risk patients, single-agent lurbinectedin was transiently leukemia suppressive for some patients, including some with abnormal chr11q or TP53 mutation. Rational combinations and situational uses of lurbinectedin are under consideration. Clinical trial information: NCT01314599.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e18521
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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