Xpovio (selinexor) / Karyopharm, Antengene, Menarini, NeoPharm, FORUS Therap, Jiangsu Hansoh Pharma - LARVOL DELTA

Comprehensive cost analysis of 4th line + therapies for relapsed/refractory multiple myeloma in Germany: Drug, co-medication, and office-based treatment perspective (ASH 2025) - "Whilst there is no official myeloma registry in Germany, treatments we considered were reimbursable combination therapies frequently used in the 4 th line treatment of RRMM in Germany in 2023, containing: carfilzomib, daratumumab, elotuzumab, melflufen, selinexor, talquetamab and teclistamab, and newly approved therapeutic options like elranatamab, along with evidence-based recommendations regarding premedication, comedication, and mandatory prophylaxis of treatment-related adverse events, as outlined in the Summary of Product Characteristics (SmPC) and published literature... Costs for myeloma drugs and combinations show a broad variation, from 88.863€ for Elotuzumab/Revlimid/Dexamethasone (ERd), to 178.850€ for talquetamab treatment. The second lowest in terms of annual costs was melflufen with 106.839€, followed by Elotuzumab/Pomalidomide/Dexamethasone (EPd):119.301€, teclistamab: 124.626€, Selinexor/Dexamethasone (Sd): 129.976€, elranatamab: 146.706€ and..."

Cost-analysis • HEOR • Hematological Malignancies • Multiple Myeloma

Synergistic effects of MALT1 inhibitor and selinexor on Acute Myeloid Leukemia cells and the underlying mechanisms (ASH 2025) - "The MALT1 inhibitor MI2 in combination with selinexor synergistically promotes apoptosis in AML cell lines by downregulating the anti-apoptotic protein Bcl-xL and inhibiting the activation of the NF-κB pathway. This strategy represents a promising therapeutic approach for treating AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • BCL2L1 • CASP3 • MALT1

Real-world treatment landscape after anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma: An international Study (ASH 2025) - "Novel BCMA-targeted therapies, such as CAR T-cells (cilta-cel from 2nd line, ide-cel from 3rd line) and bispecific T-cell engagers (e.g., teclistamab, elranatamab from 4th line), have become new standards of care...Abbreviations: K=carfilzomib; E=elotuzumab; Pom=pomalidomide; d=dexamethasone; Isa=isatuximab; F=panobinostat; R=lenalidomide; Tec=teclistamab; X=selinexor; Elra=elranatamab; Belamaf=belantamab mafodotin; Ixa=ixazomib... This real-world study of 100 MM patients relapsing after anti-BCMA CAR T-cell treatment shows that 91% were in their 4th or 5th line of therapy. A large majority were triple-class exposed, and 52% were lenalidomide-refractory. In the absence of a clear standard of care, common treatments were identified: elotuzumab- and isatuximab-based regimens in the 3rd line; teclistamab and elotuzumab-based options in the 4th line; and teclistamab, elranatamab, and belantamab mafodotin in the 5th line."

CAR T-Cell Therapy • Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Diabetes • Dyslipidemia • Hematological Malignancies • Hypertension • Metabolic Disorders • Multiple Myeloma • Renal Disease

Selinexor-based regimens in triple-class exposed or refractory multiple myeloma: A real-world analysis of efficacy and safety in 18 patients (ASH 2025) - "Treatment regimens included selinexor (40–60 mg/week) combined with the KPD regimen (carfilzomib, pomalidomide, dexamethasone) in 6/18 (33.3%) patients; other combinations comprised cytotoxic drugs, aponermin, daratumumab, and venetoclax. Selinexor-based regimens demonstrate clinically meaningful efficacy (ORR 66.7%, median PFS 10.9 months) and a manageable safety profile in heavily pretreated TCE/TCR RRMM patients. These findings support its use as a viable salvage therapy. Further validation through larger prospective trials is warranted to confirm these results."

Clinical • Real-world • Real-world evidence • Multiple Myeloma • Nephrology • Neutropenia • Plasma Cell Leukemia • Plasmacytoma • Renal Disease • Thrombocytopenia • XPO1

Real-world safety and efficacy of aponermin and selinexor-based regimens in patients with multiple myeloma (ASH 2025) - "Treatment regimens predominantly consisted of Apo+selinexor+dexamethasone (65.38%), with other combinations including Apo + daratumumab + selinexor + dexamethasone (11.54%), Apo + selinexor + carfilzomib + pomalidomide + dexamethasone (7.69%), Apo + selinexor + pomalidomide + dexamethasone (7.69%), Apo + selinexor + carfilzomib + dexamethasone (3.85%) and Apo + selinexor + cyclophosphamide + dexamethasone (3.85%). The median age was 66 years (range 29-82), with 65.38% male patients. R-ISS staging showed 11.54% stage I, 42.31% stage II, and 30.77% stage III. High-risk cytogenetic abnormalities included 1q21 gain/amplification (50.00%), t(4; 14) (19.23%), 17p deletion (15.38%) and double-hit HRCA (26.92%)."

Clinical • Real-world • Real-world evidence • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Lymphoma • Multiple Myeloma • Thrombocytopenia

Real-world safety and efficacy of aponermin and daratumumab-based regimens in patients with multiple myeloma (ASH 2025) - "Treatment regimens consisted of aponermin combined with daratumumab and various backbone therapies: dexamethasone (35.71%), selinexor-dexamethasone (28.57%), bortezomib-dexamethasone (14.29%), lenalidomide-dexamethasone (7.14%), cyclophosphamide-dexamethasone (7.14%), and carfilzomib-dexamethasone (7.14%). No hepatotoxicity was observed throughout the treatment period. Real-world data demonstrate that aponermin and daratumumab-based regimens exhibit promising efficacy and favorable safety profiles in MM patients, particularly in heavily pretreated RRMM patients, offering a potential new treatment option for this challenging population."

Clinical • IO biomarker • Real-world • Real-world evidence • Constipation • Gastroenterology • Gastrointestinal Disorder • Lymphoma • Multiple Myeloma • Thrombocytopenia

Indirect treatment comparison of belantamab mafodotin + pomalidomide + dexamethasone versus comparator regimens in lenalidomide-exposed relapsed/refractory multiple myeloma: A network meta-analysis (ASH 2025) - P3 | " In the len-exposed population, the PFS network comprised 8 RCTs (including DREAMM-8) with comparator regimens: carfilzomib + dexamethasone (Kd), Kd + daratumumab (DKd), isatuximab + carfilzomib + dexamethasone (IsaKd), bortezomib + dexamethasone (Vd), DVd, PVd, and selinexor + Vd (SVd). In the absence of head-to-head randomized controlled trials, these ITC data suggested a high probability that PFS consistently favored BPd vs comparator regimens of interest in len-exposed patients with RRMM, with consistent findings in the IPTW analysis reducing uncertainty in the base-case NMA findings."

Retrospective data • Hematological Malignancies • Multiple Myeloma

Real-world efficacy and safety of mezigdomide-dexamethasone in heavily pre-treatred multiple myeloma patients: An Italian case series (ASH 2025) - P1/2 | "Mezigdomide, a novel oral cereblon E3 ligase modulator (CELMoD), has demonstrated promising efficacy and safety in combination with dexamethasone (Mez-D) for relapsed/refractory MM (RRMM), as documented in the phase I–II trial (NCT03374085)...Prior BCMA-directed therapy included belantamab-mafodotin in monotherapy (40%), belantamab mafodotin and teclistamab (10%), or triple exposure to CAR-T cells, belantamab-mafodotin, and teclistamab (10%). Selinexor was used in 30% of cases...However, the high rate of infectious complications underlines the need for appropriate management to prevent early treatment discontinuation. These findings support the potential role of Mez-D combination in routine clinical practice, though larger prospective trials are warranted to confirm its long-term efficacy and safety, particularly in frail MM populations such as the elderly or those with renal impairment."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Pneumonia • Renal Disease • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN

Aponermin-based regimen as bridging therapy prior to CAR-T cell therapy for relapsed/refractory multiple myeloma (ASH 2025) - "He received induction therapy with the PAD regimen (bortezomib, liposomal doxorubicin, dexamethasone) and DKd regimen (daratumumab, carfilzomib, dexamethasone), achieving a Very Good Partial Response (VGPR)...Maintenance therapy with the KP regimen (carfilzomib, pomalidomide) was administered, during which surveillance studies showed minimal residual disease (MRD) negativity by bone marrow flow cytometry and negative serum and urine immunofixation electrophoresis...Bridging therapy was initiated the following day (February 23, 2025) with Aponermin (10mg/kg on Days 1-5), Selinexor (40mg once weekly), and dexamethasone (20mg once weekly)...The regimen did not adversely impact hematologic recovery following CAR-T cell infusion, and cytokine release syndrome (CRS) was mild and manageable. For patients with triple-class refractory (TCR) or penta-drug refractory multiple myeloma undergoing CAR-T cell therapy, Aponermin-based regimen represents a viable and well-tolerated..."

CAR T-Cell Therapy • Bone Marrow Transplantation • Hematological Malignancies • Inflammation • Multiple Myeloma

Therapeutic preclinical study on the synergy between CD73 inhibitors and selinexor for managing multiple myeloma (ASH 2025) - "J558 tumor-bearing BALB/c mice were randomized to receive vehicle, the CD73 inhibitor ATG-037, selinexor (ATG-010), or the combination. CD73 inhibition potentiates selinexor efficacy by selectively activating CD8⁺ T cells, thereby accelerating myeloma cell death."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • CD73 • CD8 • CD80 • ENPP1 • GZMB • IFNG

A functional precision medicine clinical trial in Relapsed/Refractory multiple myeloma: Prospective study of a high throughput drug sensitivity assay on correlation of drug sensitivity scores with treatment response (ASH 2025) - P=N/A | "All patients (100%) had prior exposure to lenalidomide, 97.5% to bortezomib, 85% to carfilzomib, 82% to daratumumab, 77.5% to pomalidomide, and 12.5% BCMA CAR-T therapy...From Oncopanel2 v1, the top drugs by DSS included bortezomib (median DSS 47.7), carfilzomib (median DSS 47.3), panobinostat (median DSS 47), and romidepsin (median DSS 45.4). From Oncopanel2 v2, the top drugs by DSS were marizomib (an investigational PI, with median DSS 46.1), carfilzomib (median DSS 40.2), ixazomib (median DSS 37.2), and oprozomib (an investigational PI, with median DSS 31.6)... The use of a high throughput drug sensitivity assay was feasible among patients with relapsed/refractory MM. In our analysis of drug-specific DSS thresholds for bortezomib and Selinexor, DSS performance varied by agent, highlighting the need for drug-specific threshold optimization. In the patients who received Selinexor, there was a non-significant tendency toward higher DSS scores in responders,..."

Clinical • IO biomarker • Hematological Malignancies • Leukemia • Multiple Myeloma • Plasma Cell Leukemia • Plasmacytoma • SDC1

Phase 3 randomized double-blind study evaluating selinexor, an XPO1 inhibitor, plus ruxolitinib in jaki-naïve myelofibrosis: Study rationale and preliminary patient characteristics (ASH 2025) - P3 | "These preliminary patient characteristics demonstrate that the population enrolled to date is consistent with those enrolled in other major phase 3 studies of MF and representative of the intended population. Higher baseline TSS may lead to more robust improvements in Abs-TSS that can better assess impacts on symptom burden in heterogenous populations across disease severity than TSS50, which is less sensitive to changes and may miss clinically meaningful changes in symptoms. Results from SENTRY will provide important insights into the effects of SEL in combination with RUX and potential benefits across key subgroups in JAKi-naïve MF, a population with continued unmet need for therapies to improve splenomegaly, symptom control and address disease modification."

Clinical • IO biomarker • P3 data • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • CALR • JAK2

Efficacy and safety of ruxolitinib-based combination therapy in the patients with myelofibrosis (MF): A systematic review and meta-analysis (ASH 2025) - "Among JAK inhibitor-naïve patients, the combination of ruxolitinib with selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by ruxolitinib plus BMS-986158 (SVR35: 90%). In addition, the efficacy ofthe combination of ruxolitinib with IFNα(SVR35:70%) and pelabresib (SVR35:66%; TSS50:53%) are also acceptable. For patients with prior JAK inhibitor exposure, ruxolitinib plus siremadlin (SVR35: 45%) and ruxolitinib plus selinexor (SVR35: 38%; TSS50: 33%) showed notable activity... For JAK inhibitor-naïve patients, ruxolitinib-based combination regimens demonstrated advantages over ruxolitinib monotherapy. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure."

Combination therapy • Retrospective data • Review • Chronic Eosinophilic Leukemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Thrombocytopenia • IFNA1

Discovery of drug combinations with momelotinib to improve myelofibrosis outcomes (ASH 2025) - "The VAF screen identified numerous inhibitors of signaling pathways operating parallel to the JAK-STAT signaling pathway including SHP2 (migoprotafib), PI3K (copanlisib), MEK (cobimetinib), agents targeting BET (BMS-986158), and STAT transcriptional targets, including BCLxL (navitoclax). The hepcidin screen identified inhibitors that combined to further suppress expression of the HiBiT transgene including CDK4 (atirmociclib) and MDM2 (navtemadlin). Notably, selinexor, an XPO1 inhibitor, combined positively with momelotinib to both kill malignant cells and suppress hepcidin expression. These results highlight several promising drug combinations that could enhance outcomes for MF patients by effectively controlling anemia and halting disease progression. These discoveries provide the scientific justification to identify optimal combination regimens aimed at addressing the multifaceted challenges of myelofibrosis."

IO biomarker • Myelofibrosis • ACVR1 • BCL2L1 • BMP6 • CDK4 • JAK1

XPO1 inhibition by selinexor blocks nucleo-cytoplasmic trafficking of multiple members of the NF-kb family in MPN cell lines and primary myelofibrosis cells (ASH 2025) - P3 | "The patient was previously treated with ruxolitinib, fedratinib, and ilginatinib/NS018, with adverse events and lack of response. Selinexor induced G0/G1 cell cycle arrest at 16 hours in HEL cells. Preliminary data showed that exposure of HEL cells to selinexor led to pronounced nuclear sequestration of several NF-κB family members. Cells with nuclear localization of RELA increased from 39.4% in DMSO-treated controls to 93.2% following selinexor treatment."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Polycythemia Vera • CD33 • CD34 • JAK2 • NFKBIA • NRAS • PTPRC • RELA • RUNX1 • SRSF2 • TET2

Overcoming asciminib resistance by targeting compound BCR::ABL1 mutations in chronic myeloid leukemia (ASH 2025) - "Selected candidate compounds demonstrating efficacy were validated across a panel of CML models, including Ba/F3 cells expressing wild-type BCR::ABL1, the T315I mutant (Ba/F3 T315I), and compound mutations (Ba/F3 PR: Y253H, E255K, and T315I), as well as K562 cells and their drug-resistant derivatives, K562 imatinib-resistant (K562 IR) and K562 ponatinib-resistant (K562 PR). CML cells with compound BCR::ABL1 mutations exhibited resistance to asciminib and, in part, to ponatinib, while bortezomib and selinexor retained efficacy in these resistant cells. Olverembatinib effectively suppressed proliferation and induced apoptosis in ABL TKI-resistant CML cells. The combination of olverembatinib and selinexor synergistically induced apoptosis and suppressed proliferation, offering a promising approach for overcoming TKI-resistant CML with compound mutations."

IO biomarker • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • CASP3 • CASP7

A real-world analysis of primary mediastinal large B-cell lymphoma: A single center study in China (ASH 2025) - "Polatuzumab vedotin, an anti-CD79b monoclonal antibody, when combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP), offers the benefits of more convenient administration and comparable safety to the R- CHOP regimen, while demonstrating reduced toxicity comparison to DA-EPOCH-R...Another patient attained CMR following R-ESHAP treatment for lymph node relapse, whereas one succumbed to CNS relapse despite receiving multiple therapies, including surgery, HD-MTX BV, selinexor, and thiotepa.5 patients received targeted therapies...Summary/Conclusion POLA-R-CHP shows potential as an efficient therapy for PMBCL. Its frontline application could enhance overall response rates while reducing treatment-related toxicity."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • Renal Disease • Respiratory Diseases • CD79B

Mechanism and therapeutic efficacy of the XPO1 inhibitor selinexor in refractory/relapsed EBV-positive NK cell lymphoma (ASH 2025) - "Overall, this study revealed the mechanism of XPO1 inhibitor selinexor targeting the IL10-JAK/STAT-MYC pathway to inhibit EBV-positive NK cell lymphoma, validating its potential as a novel therapeutic strategy for patients with relapsed/refractory EBV-positive NK cell lymphoma."

Clinical • IO biomarker • Epstein-Barr Virus Infections • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Rare Diseases • IL10 • STAT3 • XPO1

SH2B3 expression predicts selinexor sensitivity in acute myeloid leukemia (ASH 2025) - "Given that the LNK protein interacts with JAK2 and inhibits JAK-STAT signaling(Jiang J,et al 2012; Baran-Marszak F,et al 2010; Bersenev A, et al 2010; Gery S, et al2009), we hypothesize that SH2B3 's impact on selinexor sensitivity may be mediated through this pathway. Ongoing studies are investigating the mechanistic interplay between SH2B3 , JAK-STAT signaling, and XPO1 inhibition, to further refine biomarker-guided therapeutic strategies in AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • JAK2 • PLEK • SH2B3 • XPO1

Osimertinib synergizes selinexor on anti-tumor effect by targeting c-MYC in T-cell acute lymphoblastic leukemia (ASH 2025) - "Conclusions The combination of Osimertinib with Selinexor has synergistic effects on cell proliferation arrest and apoptosis in T-ALL by targeting c-MYC both in vitro and in vivo, providing a promising strategy for overcoming the treatment of T-ALL. Further clinical evaluation is required."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • EGFR • MYC • STAT3 • XPO1

Treatment with an EYA2 inhibitor prolongs survival of SIX1-expressing murine T-cell leukemias (ASH 2025) - "Intriguingly, addition of the XPO1 inhibitor KPT-330 to LG1-34 potentially enhances the inhibitory ability of LG1-34... Using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, which exploits a multiomic approach to evaluate profiles of multiple cancers, we established that increased SIX1 expression in relapsed T-ALL patients is associated with a worse event free survival (EFS) and overall survival (OS), while increased EYA2 expression is associated with worse EFS. We used the Broad Institute Cancer Dependency Map to identify that Jurkat leukemia cells, developed from a 14-year-old patient with T-ALL, had increased expression of SIX1 , but not EYA2. RT-qPCR and immunoblot validated increased SIX1 expression."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Brain Cancer • Glioma • Hematological Malignancies • Leukemia • Solid Tumor • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • KMT2A • MLLT10 • SIX1

Selinexor alone and in combination with JAK inhibitors suppresses pro-inflammatory cytokine secretion from primary myelofibrosis cells ex vivo (ASH 2025) - P3 | "In combination with ruxolitinib (RUX), SEL has shown rapid, deep, and sustained spleenand symptom responses including disease modifying potential in patients with JAK inhibitor(JAKi)–naïve myelofibrosis (MF), with associated reductions in proinflammatory cytokines(Tantravahi SK, et al...JAKis used in MF therapy, including RUX, momelotinib (MOM), and pacritinib(PAC), have limited impact on cytokine modulation... XPO1 inhibition is a potentially fundamental mechanism that addresses keyinflammatory and pathobiological features of MF. Here we demonstrate that SEL effectivelysuppresses ex vivo NF-κB–regulated pro-inflammatory cytokine production in PBMCs derivedfrom patients with MF, both as a single agent and in combination with JAKi, further validating thepotential of disease modification. The combinatory activity of XPO1 inhibition and JAK/STATinhibitors supports the clinical use of SEL plus RUX in JAKi-naïve MF, which is being evaluated inthe ongoing Phase..."

Combination therapy • IO biomarker • Preclinical • Fibrosis • Immunology • Myelofibrosis • CALR • IL6 • JAK2 • TLR8 • XPO1

Safety and efficacy of selinexor sequential azacytidine in newly diagnosed patients with myelodysplastic syndromes EB1 or EB2: A single-center, single-arm, phase ib/II trial (ASH 2025) - "Azacitidine sequential Selinexor regimen demonstrated a high response rate and wastolerable in newly diagnosed patients with MDS-EB1 or EB2. The patients with TP53 mutations had ahigher CR rate and longer PFS and OS compared with literatures. The patients who achieved CR alsoobtained high cytogenetic and molecular biology response."

Clinical • IO biomarker • P1/2 data • Anorexia • Cardiovascular • Endocrine Disorders • Heart Failure • Herpes Simplex • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia • BCOR • NPM1 • PTPN11 • RUNX1 • SF3B1 • TP53 • U2AF1 • WT1 • XPO1

Selinexor in combination with azacitidine or Ruxolitinib for Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes: A Multi-Center Prospective Exploratory Study (ASH 2025) - P2 | "The combination of selinexor with azacitidine or ruxolitinib showed good efficacy and safetyin MDS/MPN patients.Key word: Myelodysplastic/Myeloproliferative Neoplasms; Selinexor; Azacitidine; Ruxolitinib; Efficacy"

Clinical • Combination therapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • XPO1

Synergistic antitumor effects and mechanisms of KPT-330 combined with venetoclax in Acute Myeloid Leukemia (ASH 2025) - "Introduction The venetoclax-azacitidine (VA) regimen is a standard frontline therapy for elderly or chemotherapy-ineligible patients with acute myeloid leukemia (AML). These findings provide strong preclinical evidence for combining BCL-2 and XPO1 inhibitorsto address venetoclax resistance in AML. Future studies should evaluate safety and optimal dosing inclinical trials."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CASP3 • CDKN1A • MCL1