A Phase I/II Study of Selinexor (SEL) with Sorafenib in Patients (pts) with Relapsed and/or Refractory (R/R) FLT3 Mutated Acute Myeloid Leukemia (AML)

AML, selinexor, sorafenib, FLT3-mutation
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research

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Publication date: Available online 6 December 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Rafiye Ciftciler, Haluk Demiroglu, Yahya Buyukasık, Elifcan Aladag, Salih Aksu, Ibrahim C. Haznedaroglu, Nilgun Sayınalp, Osman Ozcebe, Umit Yavuz Malkan, Hakan GokerAbstractBackground and AimThe refractory acute myeloid leukemia (AML) includes patients who fail standard induction chemotherapy, relapse within 6 months after first complete remission and relapse twice or more. The outcome of these patients is usually very poor with only a small proportion could be rescued by allogenic hematopoietic stem cell transplan...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
The refractory acute myeloid leukemia (AML) includes patients who fail standard induction chemotherapy, relapse within 6 months after first complete remission and relapse twice or more. The outcome of these patients is usually very poor with only a small proportion could be rescued by allogenic hematopoietic stem cell transplantation (alloHSCT). The aim of this study is to evaluate the efficacy and feasibility of alloHSCT in patients with refractory AML.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Conditions:   Relapse or Refractory Acute Myeloid Leukemia;   Relapse or Refractory Non-Hodgkin Lymphoma;   Relapse or Refractory Multiple Myeloma Intervention:   Drug: S65487 Sponsors:   Institut de Recherches Internationales Servier;   ADIR, a Servier Group company Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusion: Liver injury associated with the autologous hematopoietic stem cell transplant, represented mainly by DILI and SOS, had a high incidence (18.9%) among the subjects in the study and was associated with an elevated mortality rate. Drug induced liver injury has been underestimated and deserves further studies.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 731. Clinical Autologous Transplantation: Results: Poster I Source Type: research
Conclusion: The rDNA transcription inhibitor CX-5461 synergises in vitro and in vivo with panobinostat, and CX-5461 retains efficacy in the setting of bortezomib-resistant myeloma.ReferencesDrygin et al., Cancer Research 2011Bywater et al., Cancer Cell 2012Quin et al, Oncotarget, 2016Devlin et al., Cancer Discovery 2016Hein et al., Blood 2017DisclosuresHarrison: Janssen-Cilag: Other: Scientific advisory board.
Source: Blood - Category: Hematology Authors: Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster I Source Type: research
Tumor cells rewire metabolic pathways to meet the high metabolic demands of proliferation, frequently developing auxotrophy to specific amino acid(s) (AAs) required to satisfy protein biosynthesis. Thus specific metabolic inhibitors or AA-depleting enzymes have been developed and tested as cancer therapeutics. For example, depletion of asparagine by bacterial L-asparaginase (ASNase) has proven efficacious against hematologic malignancies, especially leukemia and lymphoma, by starving tumors lacking asparagine synthetase (ASNS). We and others have reported that the glutaminase (GLS) activity of ASNase is required for antica...
Source: Blood - Category: Hematology Authors: Tags: Metabolism and Hematologic Malignancies Source Type: research
There is no standard therapy for patients with myelodysplastic syndromes (MDS) refractory to hypomethylating agents (HMA) and the median overall survival (OS) of HMA-refractory MDS patients with IPSS Intermediate-2/High-risk MDS is ~6 months. Here, we present data from a phase 2 clinical trial of selinexor, an oral, first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that inhibits XPO1, in patients with MDS refractory to HMAs. XPO1 is the major nuclear export protein responsible for shuttling many key cellular regulators out of the nucleus and is overexpressed in many cancers. Preclinical studies of seline...
Source: Blood - Category: Hematology Authors: Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Novel Therapeutics I Source Type: research
Background: Prior studies have demonstrated disparities in the utilization of stem cell transplant (SCT) based on age, race, and insurance type. Whether delays to SCT occur as a result of these disparities is not well established. We evaluated whether we observed similar trends in a large metropolitan SCT center with a large population of minority patients (pts).Methods: We identified pts at Karmanos Cancer Institute who had their initial SCT consultation from 2009 - 2016, and evaluated pts who received or did not receive SCT for the diagnoses of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplast...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Costs and Disparities Source Type: research
Background: BRCA1 and BCRA2 (breast cancer 1 and 2) are tumor suppressor genes involved in repair of DNA double-strand breaks. Loss of BRCA1/2 activity by (germline) mutations (mut) or downregulation (DR) of gene expression (GE) correlates with an increased risk of breast and ovarian cancer. Mut in or reduced GE of BRCA1/2 have also been implicated in some hematological malignancies, although data are so far scarce. Moreover, PARP1 inhibitors, known to induce synthetic lethality in tumors harboring BRCA1/2 mut were shown to affect FLT3(ITD)-positive AML (acute myeloid leukemia) cells.Aims: Investigation of BRCA1/2 mut and ...
Source: Blood - Category: Hematology Authors: Tags: 603. Oncogenes and Tumor Suppressors: Poster I Source Type: research
Conclusion:We confirmed the positive impact viral reactivation after allo-HSCT on relapse incidence, which could be explained as a stimulation of both function and amplification of NK compartment. Our finding about viral co-reactivation that includes EBV with a higher risk of relapse should be further explored and carefully interpreted as this might come from EBV treatment by rituximab that impairs the immunological system by impacting the GVL effect and therefore leads to more relapse.DisclosuresMichallet: Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.
Source: Blood - Category: Hematology Authors: Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster I Source Type: research
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