- |||||||||| MODULE 1: Multiple Myeloma (MM) (Hilton Chicago; Grand Ballroom (Level 2)) - May 26, 2023 - Abstract #ASCO2023ASCO_7060;
This activity is supported by educational grants from AbbVie Inc, Genentech, a member of the Roche Group, Genmab US Inc, Karyopharm Therapeutics, Lilly, Regeneron Pharmaceuticals Inc, Sanofi, and Seagen Inc. Clinical and biological factors affecting the selection of up-front therapy for patients with MMLong-term findings with daratumumab-containing regimens for newly diagnosed MM; role for transplant-eligible and ineligible patientsPublished data with novel daratumumab-based quadruplet regimens for transplant-eligible patients with newly diagnosed MMSimilarities and differences between daratumumab and isatuximabKey findings from the Phase III GMMG HD7 trial comparing isatuximab with RVd to RVd alone for transplant-eligible patients with newly diagnosed MMOngoing Phase III studies of isatuximab as a part of induction therapy for transplant-eligible and ineligible patientsAvailable data with and current role of minimal residual disease assessment in therapeutic decision-makingOptimal maintenance approach for transplant-eligible and ineligible patientsResults from Phase III trials evaluating isatuximab-based combination regimens for relapsed/refractory (R/R) MMKey results from the Phase III BOSTON trial leading to the FDA approval of selinexor in combination with bortezomib/dexamethasone for R/R MM; available data with other selinexor-based combinationsStructural makeup and manufacturing of available B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell platformsEfficacy and safety findings from the KarMMa (idecabtagene vicleucel) and CARTITUDE-1 (ciltacabtagene autoleucel) trials for R/R MMAvailable and emerging data with and ongoing studies of BCMA-targeted CAR T-cell therapies in earlier lines of treatmentSimilarities and differences in the cellular targets and mechanisms of action of bispecific antibodies in MMActivity and responses observed with available (teclistamab) and investigational (elranatamab, linvoseltamab, ABBV-383) BCMA-targeted bispecific antibodies in R/R MMBiological rationale for and available data with non-BCMA-targeted bispecific antibodies (eg, talquetamab, cevostamab, forimtamig); FDA breakthrough therapy designation for talquetamabSpectrum, incidence and severity of toxicities, including cytokine release syndrome and neurotoxicity, with bispecific antibodies in patients with MM; mitigation and management protocolsPublished data with and current role of venetoclax-based therapy for patients with MM and t(11;14) or Bcl-2 overexpressionOther promising novel strategies in clinical development for patients with MM
- |||||||||| Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
Journal: Development of Erf-Mediated Craniosynostosis and Pharmacological Amelioration. (Pubmed Central) - May 17, 2023 We treated animals with Mek1/2 and nuclear export inhibitors, U0126 and KPT-330, respectively, to increase Erf activity by two independent pathways...The treatment of mice with either the inhibitors or the administration scheme alleviated the synostosis phenotype with minimal adverse effects. Our data suggest that the ERF level is an important regulator of cranial bone development and that pharmacological modulation of its activity may represent a valid intervention approach both in CRS4 and in other syndromic forms of craniosynostosis mediated by the FGFR-RAS-ERK-ERF pathway.
- |||||||||| Removab (catumaxomab) / NeoPharm, Trion Pharma
Review, Journal: Immunotherapy for Peritoneal Carcinomatosis: Challenges and Prospective Outcomes. (Pubmed Central) - May 16, 2023 Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM...This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body.
- |||||||||| Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
ORAL REGIMEN SELINEXOR, POMALIDOMIDE, AND DEXAMETHASONE IN RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM): SAFETY ASSESSMENT AND OPTIMIZATION () - May 12, 2023 - Abstract #EHA2023EHA_2975; P2 But the initial 6 patients (XPD-60) experienced more frequent dose interruptions and/or dose reductions than patients in XPD -40 group and these patients mentioned that the adverse events of nausea and fatigue had an obviously bad influence on their quality of life even though they were mainly grade 1 or 2. This study suggests that XPD-40 regimen may be more feasible in clinical practice with comparable effectiveness and fewer adverse events which needs further exploration.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
SELINEXOR IN COMBINATION WITH VENETOCLAX AND HYPOMETHYLATING AGENTS FOR ACUTE MYELOID LEUKEMIA PATIENTS WITH SEVERE CO-MORBIDITIES () - May 12, 2023 - Abstract #EHA2023EHA_2662; P2 These results imply that the triple regimen of selinexor, venetoclax and hypomethylating agents are potentially highly effective in AML patients, even for those with serious infections or other comorbidities. Based on this preliminary result, we designed a prospective study to further evaluate the efficacy and safety of the triple regimen of selinexor, venetoclax, and azacytidine (SAV regimen) for newly diagnosed patients with AML ineligible forintensive therapy (NCT05736965).
- |||||||||| silmitasertib (CX-4945) / Senhwa Biosci, University of California, Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
SELINEXOR COMBINED WITH CX-4945 PROMOTES CELL DEATH BY TARGETING PIK3CD/AKT1/FOXO3 SIGNALING IN ACUTE MYELOID LEUKEMIA () - May 12, 2023 - Abstract #EHA2023EHA_2600; Acute myeloid leukemia, relapsed/refractory Our data demonstrated for the first time the synergistic effect of a novel combination of KPT-330 and CX-4945 on cell growth arrest and apoptosis in AML cells, and identify the underlying mechanism bytargeting the PIK3CD/AKT1/FOXO3 signaling pathway, which highlighted the feasibility of clinical trials for combination therapy of AML patients.
- |||||||||| CLINICAL OUTCOMES OF NOVEL THERAPIES IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1403;
Novel treatments for patients with R/R DLBCL include chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab vedotin plus bendamustine and rituximab (pola-BR), tafasitamab plus lenalidomide (tafa-len), loncastuximab (lonca), and selinexor. Outcomes for patients treated with pola-BR and tafa-len
- |||||||||| talquetamab (JNJ-64407564) / J&J, Blenrep (belantamab mafodotin) / GSK, Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
MATCHED-ADJUSTED INDIRECT COMPARISON OF TALQUETAMAB VS SELINEXOR-DEXAMETHASONE AND VS BELANTAMAB MAFODOTIN IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1230; P1, P2, P2 MonumenTAL-1 pts who met key eligibility criteria for STORM (triple-class refractory, refractory to last therapy, refractory to daratumumab, and penta- exposed) and DREAMM-2 (triple-class refractory and refractory to last therapy) were included in the analysis. These analyses show superior effectiveness of both talquetamab dosing schedules vs sel-dex and vs belamaf for most outcomes, and highlight talquetamab as a novel, highly effective treatment option for pts with TCE RRMM.
- |||||||||| elranatamab (PF-06863135) / Pfizer
AN INDIRECT COMPARISON OF ELRANATAMAB (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1205; P=N/A Treatment regimens in the RWD sources included various combinations of PIs, IMiDs, and mAbs, among other agents (eg, selinexor). Among TCR MM patients who resemble those of the MM-3 trial, ELRA showed improved ORR compared with treatments currently used in clinical practice.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Ninlaro (ixazomib) / Takeda, Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
ADDING REFRACTORINESS STATUS TO LINES OF THERAPY BETTER DEFINE PROGNOSIS OF A REAL LIFE ITALIAN MULTIPLE MYELOMA POPULATION (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1198; Nevertheless, RS segregated groups of patients with significantly different PFS and, particularly, OS demonstrating a higher prognostic power compared to number of LOTs. This finding could have relevant implications in designing future clinical trials.
- |||||||||| elranatamab (PF-06863135) / Pfizer
INDIRECT TREATMENT COMPARISON OF ELRANATAMAB WITH BELMAF, SEL-DEX, AND REAL-WORLD PHYSICIAN (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_1129; P=N/A, P2, While there is no standard of care for TCE MM, belantamab mafodotin (belamaf) and selinexor plus dexamethasone (sel-dex) are treatment options. Elranatamab had a significantly higher ORR than belamaf, sel-dex, and real-world PCT in LocoMMotion for patients with TCE MM, demonstrating its clear clinical benefit for this population.
- |||||||||| Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
Journal, IO biomarker: Enhance Mitochondrial Damage by Nuclear Export Inhibition to Suppress Tumor Growth and Metastasis with Increased Antitumor Properties of Macrophages. (Pubmed Central) - May 5, 2023 In this study, XPO1 inhibitor KPT-330 nanoparticles were combined with mitochondria-targeting lonidamine (TPP-LND) nanoparticles...Significantly, their combination increased the ratio of M1 tumor-associated macrophages (TAMs)/M2 TAMs both in vitro and in vivo and increased the phagocytosis of tumor cells by macrophages, thus suppressing tumor growth and metastasis. In summary, this research revealed that nuclear export inhibition can synergistically enhance the prevention of mitochondrial damage to tumor cells, heightening the antitumor properties of TAMs, thereby providing a viable and safe therapeutic approach for the treatment of tumor metastasis.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
Journal, Combination therapy, PD(L)-1 Biomarker, IO biomarker, Metastases: Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non-small cell lung cancer. (Pubmed Central) - May 2, 2023 P1 Selective inhibitors of nuclear export proteins, such as selinexor, can induce restoration of tumor-suppressing pathways and induce potent immunomodulatory activities. This article contains the clinical safety and early efficacy data on the combination of pembrolizumab and selinexor in treatment of metastatic non-small cell lung cancer.
- |||||||||| Xpovio (selinexor) / Karyopharm, Menarini, FORUS Therap
Targeting Exportin 1 as treatment for cutaneous squamous cell carcinoma. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_6625; Additionally, cSCC cells had lower IC50 values for Selinexor, suggesting cSCC may be more sensitive to XPO1 inhibition compared to normal keratinocytes. Further, targeting XPO1 also increases apoptosis in these cells.
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