Glucocorticoid Receptor 

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  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Arranon (nelarabine) / Novartis
    Pharmacotypes across the Genomic Landscape of Pediatric Acute Lymphoblastic Leukemia and Impact on Treatment Response (ENMCC - Great Hall BC) -  Nov 4, 2022 - Abstract #ASH2022ASH_5067;    
    LC50s of prednisolone, asparaginase, and mercaptopurine were associated with age, and/or with leukocyte count at diagnosis...In B-ALL, sensitivities of prednisolone, asparaginase, dexamethasone, cytarabine and thiopurines were positively correlated with MRD...Instead, sensitivities of dasatinib and nelarabine correlated positively, and venetoclax negatively, with MRD in T-ALL...CONCLUSION Ex vivo drug sensitivities vary widely across ALL subtypes and strongly influence in vivo MRD. Our study comprehensively described pharmacological heterogeneity of ALL and the association of drug sensitivities with survival outcomes, providing insight into the pharmacological basis of inter-patient variability in ALL treatment outcomes and highlighting opportunities for individualizing therapy for this blood cancer.
  • ||||||||||  dexamethasone / Generic mfg., prednisone / Generic mfg.
    A Transcriptional Classifier Identifies Pediatric T-Cell Acute Lymphoblastic Leukemias at High Risk for End of Induction Minimal Residual Disease (ENMCC - Great Hall BC) -  Nov 4, 2022 - Abstract #ASH2022ASH_5064;    
    In conclusion, while ETP samples are commonly MRD+ and are readily identifiable by their unique cell surface immunophenotype, non-ETP samples lack a surface immunophenotype that correlates with MRD+. Here, we present a targeted gene expression classifier, validated on a clinically-tractable platform, that identifies at diagnosis a subset of non-ETP T-ALLs with a gene expression pattern that resembles that of ETP T-ALLs and that are at high risk for future MRD+.
  • ||||||||||  Is VTD the Best First Line Therapy for Multiple Myeloma in an Environment with Limited Resources? an Analysis of Outcomes and Costs (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4820;    
    Patients with MM treated between 2017 and 2019 with 4 cycles of VTD (Bortezomib, thalidomide, dexamethasone) followed by auto-HSCT and maintenance with thalidomide were included...Conditioning was melphalan 200 mg/m2 in n=35 (79.5%)...Table 1 compares the costs of 4 induction cycles with usual scheme CONCLUSIONS The response with VTD followed by auto-HSCT and maintenance with thalidomide are comparable in overall and progression-free survival with more expensive schemes such as KRd, VRd and Dara-VTd with lower cost. Key words: stem cell trasplantation, multiple myeloma, cost, limited resource
  • ||||||||||  Does Choice of Salvage Regimen Impact Stem Cell Mobilization in Hodgkin's Lymphoma? (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4749;    
    Although, PBSC collection and subsequent ASCT was eventually successful in a majority of the patients in the BBV group, two patients in our population failed to undergo ASCT given inadequate mobilization/collection. With the increasing utilization of brentuximab-vedotin in salvage as well as in the first line setting, larger studies are needed to study its impact on PBSC collection and ASCT.
  • ||||||||||  Abecma (idecabtagene vicleucel) / BMS, 2seventy bio
    KarMMa-2 Cohort 2c: Efficacy and Safety of Idecabtagene Vicleucel in Patients with Clinical High-Risk Multiple Myeloma Due to Inadequate Response to Frontline Autologous Stem Cell Transplantation (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4695;    
    P2
    Methods Eligible pts in cohort 2c had newly diagnosed MM (NDMM), received =3 cycles of induction therapy (including a proteasome inhibitor, immunomodulatory agent, and dexamethasone), and had an inadequate response to ASCT (single or tandem), defined as less than very good partial response (VGPR) at 70–110 days after last ASCT, without use of consolidation or maintenance therapy...After lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 × 3), pts received a single infusion of ide-cel at dose range 150–450 × 106 CAR+ T cells...Early deep clearance of tumor was seen in pts with =CR after ide-cel treatment and was sustained at 2 y. Lower incidence of CRS and NT were seen in these pts vs those treated with ide-cel in later lines. These results support a favorable clinical benefit-risk profile of ide-cel in NDMM.
  • ||||||||||  Darzalex (daratumumab) / J&J
    Therapeutic Outcomes of Relapsed-Refractory Multiple Myeloma Patients with 1q21+Treated with Daratumumab-Based Regimens: A Retrospective Analysis (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4597;    
    While there is emerging data that Isa-based regimens can improve the PFS and ORR of patients with RRMM with 1q21+, we noted that for RRMM pts treated with Dara-based regimens, outcomes for pts with 1q21+ are similar to those with standard risk disease or other HRCyto markers. The lack of PFS and ORR differences seen regardless of 1q21+ status with Dara-based regimens could suggest that Dara-based treatment may abrogate the poor outcomes associated with the presence of 1q21+.
  • ||||||||||  Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
    Real World Efficacy and Toxicity of Selinexor: Importance of Dose Intensity and Post Progression Outcomes (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4558;    
    Selinexor is the first in class, orally available, exportin inhibitor, approved for heavily pretreated, triple class refractory myeloma patients (pts) in combination with dexamethasone (Sd) and in pts with relapsed/refractory myeloma (RRMM) with 1-3 prior lines of therapy in combination with bortezomib and dexamethasone (SVd)...All pts were refractory to lenalidomide and exposed to PIs, 91% were refractory to =one PI (70% to carfilzomib), 86% to pomalidomide, 93% to anti-CD38 monoclonal antibody and 34% (15/44) to anti-BCMA therapy...After progression to Sd/SVd, 20 pts received further therapy; they had a median of 7 prior lines (range 5-13) and their treatment included belantamab mafodotin in 4, anti-CD38-containing in 2, PIs+/- chemo in 6, PIs with IMiDs in 2, IMiDs +/- chemo in 3, Sd with added PI in 2 and one received chemo alone...Dose adjustments are required in most pts indicating that optimal dose of selinexor may be lower than the recommended. The prognostic impact of low serum albumin in these pts needs further evaluation as it may be a marker of poor nutrition, advanced disease and poor tolerance to selinexor.
  • ||||||||||  bortezomib / Generic mfg.
    African American Race As a Risk Factor for Developing Peripheral Neuropathy in Newly Diagnosed Patients with Multiple Myeloma Receiving Bortezomib Induction (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4550;    
    We identified a cohort of 748 newly diagnosed MM patients who received at least one full cycle of bortezomib as part of induction with bortezomib, lenalidomide, and dexamethasone (RVd) at the Winship Cancer Institute at Emory University from 2007-2016...By logistic regression model, the incidence of BIPN was higher in AA patients in both univariate (odds ratio, 1.61; 95% CI: 1.00-2.61; p=0.052) and multivariable analyses (odds ratio, 1.64; 95% CI 1.01-2.67; p=0.047). These data indicate that AA race is an independent risk factor for the development of BIPN.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, IACS-010759 / UT MD Anderson Cancer Center, navitoclax (ABT 263) / AbbVie
    LP-118, a Novel BCL2 Inhibitor, Shows Potent in Vitro Anti-Myeloma Activity (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4548;    
    P1
    However, best results were seen when targeting the compensatory upregulation of MCL-1 with S63845, an MCL-1 inhibitor...An ongoing phase 1 dose-escalation trial (NCT04771572) is underway evaluating safety and tolerability in patients with relapsed or refractory hematological malignancies. Future in vitro and in vivo animal studies will continue to evaluate drug combinations that best overcome drug resistance to anti-apoptotic treatment.
  • ||||||||||  Darzalex (daratumumab) / J&J
    The Mutagenic Impact of Radiotherapy in Multiple Myeloma (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4546;    
    However, in contrast to chemotherapy mutational signatures (e.g. melphalan, SBS-MM1; and platinum, SBS31), the ID8 mutational process has additional intrinsic components and can be found in RT-naïve tumors with defects of DNA double-strand break repair by non-homologous DNA end-joining and with mutations in topoisomerase TOP2A (Alexandrov et al...As a validation group, we included WGS from 58 NDMM patients treated with Carfilzomib/Lenalidomide/Dexamethasone +/- Daratumumab (Landgren et al., JAMA Onc, 2021; Korde et al., JAMA Onc 2015)...Comparisons computed with Wilcoxon Rank Sum test. SR, Standard Risk; HR, High Risk; ND, Newly Diagnosed; RR, Relapsed/Refractory; RT, Radiotherapy.
  • ||||||||||  dexamethasone / Generic mfg.
    Metabolic Feature Profiling and Metabolic Vulnerability Targeting in B-Cell Lymphoblastic Leukemia (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4263;    
    In summary, by integrating multi-center and multi-omics B-ALL data, our research innovatively established and verified a novel metabolic classification system of B-ALL, which revealed that metabolic preferences and dependencies have important prognostic significance in B-ALL. By deciphering metabolic characteristics and metabolic fragility of B-ALL, it is expected to achieve targeted therapy for the metabolic fragility and improve clinical prognosis.