Glucocorticoid Receptor 

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  • ||||||||||  Darzalex (daratumumab) / J&J
    A Phase 2 Study of Daratumumab in Combination with Thalidomide and Dexamethasone in Relapsed and / or Refractory Myeloma: A Report from the Asian Myeloma Network (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2440;    
    They appear synergistic with immunomodulatory drugs; triplet combinations with lenalidomide 1 (DRd) or pomalidomide 2 (DPd) and dexamethasone have been approved for treatment of RRMM...91% of patients had prior exposure to bortezomib, while 88% had prior exposure to thalidomide, lenalidomide or both...Conclusion The combination of daratumumab, thalidomide and dexamethasone is effective in RRMM patients. Thalidomide and dexamethasone are cost-effective drugs which can improve the accessibility of daratumumab-based triplet combinations.
  • ||||||||||  Actemra IV (tocilizumab) / Roche, JW Pharma, Tecvayli (teclistamab) / Genmab, J&J
    Prophylactic Tocilizumab to Prevent Cytokine Release Syndrome (CRS) with Teclistamab Administration (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2439;    
    Prophylactic tocilizumab prevented usage of steroids, prevented dose delays, prevented readmission to the hospital, and possibly reduced the occurrence of ICANS. These data make a case for early incorporation of prophylactic tocilizumab and support outpatient administration of teclistamab in most patients.
  • ||||||||||  Empliciti (elotuzumab) / AbbVie, BMS
    Immunological Subgroups Predicting Efficacy of Elotuzumab in Multiple Myeloma Patients: Insights from the GMMG-HD6 Clinical Trial (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2421;    
    P3
    The trial investigated elotuzumab in combination with lenalidomide/bortezomib/dexamethasone induction and consolidation, followed by lenalidomide maintenance in transplant-eligible newly diagnosed MM patients and found no progression-free or overall survival advantage with the addition of elotuzumab in any treatment sequence. As high levels of regulatory CD8 + T cells showed adverse progression-free survival in MM patients, the assessment of the level of regulatory CD8 + SLAMF7 + T cells could be a prerequisite for MM patients
  • ||||||||||  Darzalex (daratumumab) / J&J
    Efficacy of Daratumumab-Based Regimens in Anti-CD38 Treatment-Na (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2415;    
    Daratumumab was combined with bortezomib/dexamethasone (DVd), carfilzomib/dexamethasone (DKd), and pomalidomide/dexamethasone (DPd) for treatment of RRMM...Eighty-eight patients (80%) were lenalidomide refractory, while 53 patients (48%) had double refractory disease to both a PI and IMiD treatment...Conclusion : Advanced stage R-ISS disease at diagnosis, presence of -17/del(17p), and 2 or more HC abnormalities were associated with poor prognosis reflected by worse PFS and OS in HC-RRMM treated with daratumumab-based therapies. A larger cohort or a prospective study in patients with HC-RRMM is needed to compare long-term outcomes between daratumumab-based therapies (DKd, DVd, and DPd).
  • ||||||||||  Darzalex (daratumumab) / J&J
    Genomic and Immune Determinants of Resistance to Anti-CD38 MoAb Based Therapy in Relapsed Multiple Myeloma (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2396;    
    P=N/A
    To characterize the genomic and immune microenvironment factors associated with resistance to daratumumab, lenalidomide and dexamethasone (dara-Rd), we integrated whole genome sequencing (WGS) and flowcytometry data generated from a longitudinally cohort (N=32) of relapsed/refractory MM (RRMM) patients (NCT03848676). Overall our data revealed that the MM resistance and progression to dara-Rd in RRMM patients is driven by a complex interplay between high genomic complexity and an immune-exhausted microenvironment.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Farydak (panobinostat) / Secura Bio, Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
    Transcriptomic Features Influencing Anti-Myeloma Drug Resistance in Human Multiple Myeloma Cell Lines (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2372;    
    With the rapid evolution of protein-protein interaction inhibitors, future exploration of KEAP1-NRF2 or MDM2-TP53 interaction inhibitors could potentially enhance myeloma cell sensitivity. In the future, our team plans to expand the drug panel used in the screen and provide this enriched dataset as a public resource, thereby facilitating wider access and collaborative advancements in the field.
  • ||||||||||  bortezomib / Generic mfg., dexamethasone / Generic mfg.
    IRF4-BLOC1S5, the First Genomic Fusion Gene Identified in the TEMPI Syndrome (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2352;    
    More molecular events responsible for the TEMPI syndrome still await to be identified, albeit a ultrarare occurrence of this disease. An intensive international collaboration is strongly proposed to completely elucidate its molecular mechanisms.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
    Retrospective Review of Patients Treated with Intrathecal Rituximab for Primary and Secondary CNS Lymphoma and Leukemia (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2194;    
    This patient developed tightening of the throat, flushing, and toe numbness after the first IT rituximab and symptoms resolved with administration of hydrocortisone and diphenhydramine. The use of IT rituximab appears safe and showed promising activity in B cell malignancies, specifically as part of induction in patients with leptomeningeal disease and PCNSL as those patients achieved cytologic response.
  • ||||||||||  Actemra IV (tocilizumab) / Roche, JW Pharma, Epkinly (epcoritamab-bysp) / Genmab, AbbVie
    Mitigating the Risk of Cytokine Release Syndrome (CRS): Preliminary Results from a DLBCL Cohort of Epcore NHL-1 (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2149;    
    P1/2
    The study treatment plan includes a mandatory prephase with prednisolone or dexamethasone followed by 12 treatment cycles of 3 weeks each (Fig...The step-up cycle (cycle 1) is comprised of intravenous (i.v.) application of obinutuzumab 1000 mg on D1, followed by i.v. application of polatuzumab vedotin 1.8 mg/kg on D2 and i.v. application of glofitamab in escalating doses of 2.5 mg on D8 and 10 mg on D15...We observed 34 adverse events (AEs) including infections (6/10 patients; grade 1: 2; grade 2: 2; grade 3:2; no grade 4/5), neuropsychiatric issues (prednisone induced psychosis, fatigue, dysgeusia (4/10; all grade 1), CRS (3/10; all grade 1), cardiovascular side effects (3/10; all grade 2), infusion related reactions (2/10; grade 2), anemia (1/10; grade 2), bleeding (1/10; grade 3), and renal toxicity (1/10; grade 3)...Study sponsor of R-Pola-Glo (EudraCT No.: 2022-003398-51) is the Institut f Background: Epcoritamab SC, a CD3xCD20 T-cell
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche, Imbruvica (ibrutinib) / AbbVie, J&J
    Prospective Evaluation of Minimal Residual Disease in Waldenstr (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_2037;    
    P=N/A
    The median follow-up for the whole series was 41 months, resulting in a 3-years PFS of 71% and 3-years OS of 89%, respectively. Interestingly, despite the current limited follow-up for such an indolent disease, MRD positivity by ddPCR in PB predicted a dismal clinical outcome if compared with MRD negative patients (3-years PFS 40% vs 73%, p=0.038).
  • ||||||||||  Jakafi (ruxolitinib) / Novartis, Incyte
    Improved Prevention and Treatment Strategy of Differentiation Syndrome Contribute to Reduce Early Death of Patients with Acute Promyelocytic Leukemia (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_1940;    
    P4
    Purpose: All-trans retinoic acid (ATRA) with arsenic trioxide (ATO) has been the standard of care for acute promyelocytic leukemia (APL) with high efficacy in china.However,early death (ED) still remains the major reason for treatment failure.Severe differentiation syndrome (DS) with no response to full dose dexamethasone is one of direct or indirect important causes of ED.Therefore,to further optimize prevention and treatment strategy of DS is critical for APL therapy success...During the course of induction therapy,we used different intravenous doses of dexamethasone to prevent DS according to the WBC count at presentation or after the initiation of ATRA.For example,if WBC counts= 5*10 9 /l and <10*10 9 /l,5mg per day;if = 10 *10 9 /l,10mg per day.And we gave patients dexamethasone 10mg per 12h as preemptive therapy once DS was suspected.Ruxolitinib was administered when steroids therapy were considerd insensitive... Our study suggests individualized steroids prevention,preemptive treatment and Ruxolitinib as second-line therapy for DS contribute to control DS,which in verse lessen the discontinuation of ATRA, consequently decreasing early death due to DS and hemorrhage in APL patients.(clinicaltrials.gov NCT04446806) Keywords: acute promyelocytic leukemia;early death;prophylaxis strategy;pulmonary hemorrhage;differentiation syndrome;retinoid acid syndrome;Ruxolitinib;steroid-resistance;cytokine release syndrome;
  • ||||||||||  Blincyto (blinatumomab) / Astellas, Amgen
    Chemotherapy-Sparing Induction Followed By Consolidation and Maintenance with Blinatumomab and Concurrent Oral Tyrosine Kinase Inhibitor Therapy for Newly-Diagnosed Philadelphia Chromosome-P... (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_1921;    
    P2
    Induction (IND) w/ corticosteroids (CS) and dasatinib (DAS) alone results in morphologic complete response (mCR) rates approaching 100% but low rates of measurable residual disease (MRD) negativity; addition of intensive chemotherapy to TKIs adds risks of myelosuppression...Pts received CS pre-phase w/ prednisone (PRED) or dexamethasone (DEX) followed by modified GIMEMA LAL1205 IND (DEX + DAS 140 mg/d w/ DAS dose adjustments or TKI change per protocol) w/ intrathecal methotrexate (IT MTX) d22, 43 and bone marrow (BM) MRD assessments including FACS and BCR::ABL1 PCR...All began DAS 140 mg/d as initial TKI; 4 changed TKI for DAS intolerance per protocol (bosutinib, n=2; ponatinib [PON], n=2) and remained on study; TKI was changed to PON in 1 other pt to optimize BCR::ABL1 transcript suppression pre-allogeneic transplant (alloHCT) and that pt was withdrawn from study...Use of PON (vs DAS) as initial TKI w/ BLIN may further suppress resistant clones. Further f/u is needed to confirm durability of CMR w/ BLIN + TKI CONSOL
  • ||||||||||  Idhifa (enasidenib) / BMS, Servier, Tibsovo (ivosidenib) / Servier, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
    Changes in White Blood Cell Counts Early during Treatment of Acute Leukemia Using Differentiating Chemotherapies (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_1896;    
    Our analysis revealed that 26% (18/68) of patients had clinical documentation of differentiation syndrome, including 21% (14/33) of patients treated with ATRA+Arsenic and 11% (4/35) of patients on IDH inhibitors. In APL, the median day of a recorded diagnosis of DS was 4 days after treatment start (range 1-14 days).
  • ||||||||||  arsenic trioxide / Generic mfg.
    Impact of Arsenic Trioxide in the Treatment of Higher Risk Acute Promyelocytic Leukemia (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_1881;    
    The toxicity profile of ATO was acceptable. Combining ATO and ATRA limits the use of cytotoxic chemotherapy, which could reduce myelosuppression and long-term complications such as cardiotoxicity and secondary myeloid neoplasms.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Darzalex (daratumumab) / J&J
    Venetoclax in Combination with Daratumumab and Dexamethasone Elicits Deep, Durable Responses in Patients with t(11;14) Relapsed/Refractory Multiple Myeloma: Updated Analyses of Minimal Resid... (Grand Hyatt - Harbor Ballroom) -  Nov 3, 2023 - Abstract #ASH2023ASH_1391;    
    P2
    Here, we report updated analyses of minimal residual disease (MRD) negativity from the Phase 1/2 trial of VenDd at 400 and 800 mg Ven dose levels, versus bortezomib plus Dd (DVd) in patients with t(11;14)-positive RRMM...A total of 80 patients were enrolled (Parts 1 and 3 combined); 55 patients received VenDd (24% high-risk cytogenetics, 53% 1 prior LOT, 2% prior anti-CD38 monoclonal antibody [mAb], 76% lenalidomide-refractory); and 26 received DVd (23% high-risk cytogenetics, 38% 1 prior LOT, 4% anti-CD38 mAb, 92% lenalidomide-refractory)... VenDd treatment showed higher rates of MRD-negativity and sustained MRD-negativity compared to DVd in patients with t(11;14)-positive RRMM, which was associated with longer PFS with VenDd.
  • ||||||||||  Tecvayli (teclistamab) / Genmab, J&J
    Outpatient Management of CAR-T and Teclistamab for Patients with Lymphoma and Multiple Myeloma (Marriott Marquis - Marriott Grand) -  Nov 3, 2023 - Abstract #ASH2023ASH_1283;    
    The rate of second CRS event after management of first CRS with steroid (dexamethasone/ prednisone) was 15% (2/13)... Our data showed that additional advances in outpatient practice, including initial outpatient management of CRS and outpatient administration of Tec step up dosing are feasible, safe and reduce hospital resource utilization.
  • ||||||||||  Quantitative MYD88 L265P Analysis Represents a Powerful Tool for Assessing Disease Response and Evaluating Clinical Trial Performance in Waldenstrom (Grand Hyatt - Seaport Ballroom EFGH) -  Nov 3, 2023 - Abstract #ASH2023ASH_1234;    
    P1/2, P2
    In contrast, minimal changes in BM and PB MYD88 L265P ?Ct from baseline were observed at best response for most major responders on IBR or IBR/ULO, including individuals who achieved very good partial responses denoted by > 90% decrease in IgM by IWWM-11 criteria. In this first prospective evaluation of BM and PB qMYD88 L265P response assessment, we show that both BM and PB L265P qMYD88 analysis can provide more accurate assessment of treatment related changes in disease burden over the current standard of IgM response assessment alone, and can be used to more robustly evaluate clinical trial performance by identifying treatments or regimens that produce more meaningful tumor reductions in WM patients.