- |||||||||| Xpovio (selinexor) / Karyopharm
HMGB3 As a Cargo Protein for XPO1: Implications for Myelodysplastic Syndromes Prognosis and Treatment (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5705; In summary, we identified HMGB3 as a novel cargo protein for XPO1 and demonstrated that HMGB3 acts as a tumor suppressor gene in MDS. HMGB3 induces panoptosis in synergy with selinexor by activating the cytoplasmic DNA sensing signaling pathway, thereby inhibiting the progression of high-risk MDS.
- |||||||||| Xpovio (selinexor) / Karyopharm
Renal Response of Selinexor, Pomalidomide, Bortezomib and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients with Renal Impairment: Preliminary Analysis from a Phase 2, Prospective, Multicenter Study (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5603; P2 Renal Response of Pomalidomide with Bortezomib and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients with Renal Impairment: A Prospective, Open-Label, Multicenter, Phase 2 Study [J]. Blood, 2022, 140(Supplement 1): 10167-9
- |||||||||| ziftomenib (KO-539) / Kura Oncology, Xpovio (selinexor) / Karyopharm
Combined Use of Ziftomenib and Selinexor Is Effective in NPM1 Mutant Acute Myeloid Leukemia (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5285; This preclinical study supports the robust synergy of ziftomenib and XPO1 inhibition beyond KMT2A-r and could be a potential strategy for treating NPM1-mutant AML. The synergy we demonstrated in KMT2A-r and NPM1-mutant models sets a premise for translational potential.
- |||||||||| Xpovio (selinexor) / Karyopharm
Selinexor Induces DLBCL Cell Senescence Mediated By USP1/MDMX/p53 Axis (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5228; We demonstrated that the treatment of Selinexor could promote p53 protein stability to further induce a senescence-like state in DLBCL cells by regulating the USP1/MDMX/p53 axis. Overall, this study highlights that reactivating p53 play important roles in the treatment of Selinexor for DLBCL patients.
- |||||||||| Cancer Pathway Connectivity Resolved By Drug Perturbation and RNA Sequencing (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3874;
In conclusion, the addition of targeted pathway perturbations to the GEP of primary CLL samples can greatly enhance the potential for molecular and functional classification of disease and subgroups. Our study provides a blueprint to use perturbed omics profiling and interaction testing to link disease drivers to pathway activation and function.
- |||||||||| P-BCMA-101 / Poseida Therap, Talvey (talquetamab-tgvs) / J&J
Late Polyclonal P-BCMA-101 CAR-T Cell Re-Expansion and Rapid Complete Response in a Patient with Relapsed Multiple Myeloma Treated with One Cycle of Talquetamab, More Than 3 Years after CAR-T Infusion (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3806; Here, we report a case of a 57-year-old female with RRMM who initially received P-BCMA-101, a TSCM rich autologous CAR-T manufactured using the piggyBac DNA delivery system, on 8/24/20 in combination with Rituximab (375 mg/m2 on days -12, -5 and then every 8 weeks for 10 cycles) and LD (cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day on days -5, -4 and -3)...She was treated with Daratumumab, Pomalidomide and dexamethasone for ~7 months with stable disease and then Selinexor and dexamethasone for 2 months which was poorly tolerated...This is the first such report of a transposon manufactured TSCM rich CAR-T showing late and dramatic re-expansion following exposure to a TCE. This case also demonstrates that T-cell proliferations following CAR-T therapy may not always be malignant and thorough molecular analysis beyond what is the clinical standard is necessary to rule out benign processes.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Venetoclax Enhances Human ??t Cells Anti-Leukemia Immunity through Metabolic Reprogramming (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3757; Combining Venetoclax with ??T cells decreased tumor burden in THP-1-bearing mice. We found upregulated activation markers CD25 and CD69 and cytotoxic molecules NKG2D and DNAM-1 on drug-treated ??T cells when these cells were exposed to tumor targets.
- |||||||||| Xpovio (selinexor) / Karyopharm
Selinexor Reduces the Immunosuppressive Properties of Macrophages and Synergizes with CD19 CAR-T Cells Against B-Cell Lymphoma (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3667; P1 We found upregulated activation markers CD25 and CD69 and cytotoxic molecules NKG2D and DNAM-1 on drug-treated ??T cells when these cells were exposed to tumor targets. Our study demonstrated that SEL could mitigate the immunosuppression of macrophages and improve CAR-T cell functionality, and the sequential administration of SEL and CAR-T cells was more effective in BCL.
- |||||||||| Patterns of Use and Outcomes of Novel Agents in Patients with Relapsed or Refractory Large B-Cell Lymphoma: A Single-Center Retrospective Analysis (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3098;
The updated findings demonstrate comparable effectiveness to our previous study, and the positive clinical outcome indicates that the selinexor combination could be a potential treatment option for R/R TP53-altered DLBCL Introduction In addition to chimeric antigen receptor T-cell therapy (CAR-T), 6 novel agents are approved in the United States for relapsed/refractory (r/r) large B-cell lymphoma (LBCL): polatuzumab (pola) in combination with bendamustine (B) and rituximab (R), tafasitamab plus lenalidomide (tafa/len), loncastuximab (lonca), selinexor, and two CD3xCD20 bispecific antibodies (BsAb) (epcoritamab and glofitamab)...Pola (alone or with R
- |||||||||| Xpovio (selinexor) / Karyopharm
KPT-330 Combined with Radiation Therapy: Effective Central Nervous System Lymphoma Treatment with Reduced Neurotoxicity (Ballroom 20CD (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2047; Our findings demonstrate that combining KPT-330 with IR can lower radiation doses while more effectively suppressing central nervous system lymphoma compared to higher dose-rate irradiation, and with reduced risk of normal tissue toxicities. This presents an encouraging clinical prospect that is poised to stimulate further investigation into CNSL radiation therapy.
- |||||||||| Xpovio (selinexor) / Karyopharm
Single Cell Atlas of Cutaneous T Cell Lymphomas Reveals XPO1 Dependency (Pacific Ballroom Salons 18-19 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_1972; Patients with high-risk disease (LCT, advanced-stage) harbor malignant T cells that are highly enriched in eIF4E/XPO1 dependent transcripts. Therefore, the eIF4E/XPO1 axis is a novel dependency and therapeutic target in CTCL.
- |||||||||| Unraveling Molecular Subgroup-Specific Pathway Dependencies in Chronic Lymphocytic Leukemia through Drug-Perturbed Transcriptomic Profiling and Statistical Modeling (Room 6DE (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_1776;
Conversely, perturbations like BTK inhibition by ibrutinib, PI3K inhibition by duvelisib, and mTOR inhibition by everolimus were linked to multiple factors shared across perturbations, suggesting extensive downstream pathway cross-talks...This study underscores the value of perturbed transcriptomic profiling of primary cancer patient samples for mapping detailed pathway structures and dependencies on disease drivers. Our comprehensive computational workflow serves as a guide for mining and interpreting complex high-dimensional data, advancing our understanding of disease biology, and facilitating the rational design of novel personalized therapies, including combinational treatments.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi, Lymphoglobuline (equine anti-thymocyte globulin) / Sanofi, Grafalon (rabbit anti-T-lymphocyte globulin) / Mundipharma, NeoPharm
Journal: A Comparative Analysis of Low Dose Grafalon (Pubmed Central) - Nov 4, 2024 Due to the shift of donor preference to alternate donors, reliance on rabbit-ATG (rATG) has increased. In our study, Grafalon
- |||||||||| Xpovio (selinexor) / Karyopharm
ENGOT-EN20/GOG-3083/XPORT-EC-042 A PHASE 3, randomized, placebo-controlled, double-blind, multicenter trial of Selinexor in maintenance therapy for patients with p53 wild-type, advanced or recurrent endometrial carcinoma (Halls 1 & 2) - Nov 3, 2024 - Abstract #COSA2024COSA_470; P3 Current Trial Status: Patient enrollment is ongoing internationally, including at the following ANZGOG sites (as of 27th June 2024). NSW: Border Medical Oncology, Gosford Hospital and Wyong Hospital, Chris O'Brien Lifehouse, Newcastle Private Hospital QLD: ICON Cancer Centre Southport, Toowoomba Hospital SA: Royal Adelaide Hospital TAS: Royal Hobart Hospital VIC: Cabrini Malvern and Cabrini Brighton, Frankston Hospital, Monash Health, Peter MacCallum Cancer Centre.
- |||||||||| Xpovio (selinexor) / Karyopharm
Preclinical, Journal: Spatial memory in Alzheimer's disease 5XFAD mice is enhanced by XPO1 inhibitor KPT-330. (Pubmed Central) - Nov 1, 2024 Unexpectedly, general amyloid deposition in several brain regions was significantly increased by KPT-330, but specific regions, especially the thalamus, displayed significantly lower deposition, suggesting that XPO1 inhibition has regional-specific effects on proteostasis and amyloid plaque formation. Altogether, we conclude that XPO1 inhibition can improve cognition via spatially-specific reductions in amyloid deposition.
- |||||||||| Darzalex (daratumumab) / J&J, Xpovio (selinexor) / Karyopharm
Journal, IO biomarker: The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma. (Pubmed Central) - Oct 30, 2024 The analysis further revealed that daratumumab and selinexor have anti-correlated mechanisms of resistance, and treatment with a selinexor-based regimen immediately after a daratumumab-containing regimen was associated with improved survival in three independent clinical trials, supporting an evolutionary-based strategy involving sequential therapy. These findings suggest that this unique repository and computational framework can be leveraged to inform underlying biology and to identify therapeutic strategies to improve treatment of MM.
- |||||||||| Empliciti (elotuzumab) / AbbVie, BMS, Xpovio (selinexor) / Karyopharm
Enrollment open, Enrollment change: XPORT-MM-031: A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple Myeloma (clinicaltrials.gov) - Oct 27, 2024 P3, N=222, Recruiting, Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2024 Active, not recruiting --> Recruiting | N=109 --> 222
- |||||||||| Xpovio (selinexor) / Karyopharm
Journal, IO biomarker: NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation. (Pubmed Central) - Oct 24, 2024 The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions...Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 and menin may be a promising strategy for the NPM1-rearranged AML.
- |||||||||| Xpovio (selinexor) / Karyopharm
Journal: Allosteric degraders induce CRL5 ASB8 mediated degradation of XPO1. (Pubmed Central) - Oct 17, 2024 Selinexor/KPT-185 is an allosteric degrader. We have explained how drug-induced protein degradation is mediated by a CRL5 system through an allosteric rather than a molecular glue mechanism, expanding the modes of targeted protein degradation beyond the well-known molecular glues of CRL4.
- |||||||||| Empliciti (elotuzumab) / AbbVie, BMS, Xpovio (selinexor) / Karyopharm
Enrollment closed, Enrollment change: XPORT-MM-031: A Study of Combination of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Subject With Previously Treated Multiple Myeloma (clinicaltrials.gov) - Oct 15, 2024 P3, N=109, Active, not recruiting, In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients. Recruiting --> Active, not recruiting | N=222 --> 109
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