Ninlaro (ixazomib) / Takeda - LARVOL DELTA

Balancing the Risk of Cardiotoxicity Outcomes in Treatment Selection for Multiple Myeloma: A Retrospective Multicenter Evaluation of Ixazomib, Lenalidomide, and Dexamethasone (IRd) Versus Carfilzomib, Lenalidomide, and Dexamethasone (KRd). (PubMed, EJHaem) - "After propensity-score-matching 478 patients from each cohort, the onset of new heart failure (HR 0.25; p < 0.001) and arrhythmias (HR 0.57; p = 0.014) at 6 months were significantly lower with IRd while overall survival at 3 years was similar (p = 0.50). IRd is associated with a significantly lower risk of cardiac toxicities compared to KRd."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Multiple Myeloma • Oncology

Cost-Utility Analysis of Sequential Therapy of iCT IRd and DRd strategy for Newly Diagnosed Multiple Myeloma Patients Who are Transplant-Ineligible in China (ISPOR 2025) - "OBJECTIVES: The iCT IRd strategy (in-class transition from bortezomib-based induction regimens to ixazomib-lenalidomide-dexamethasone regimen) and the DRd strategy (daratumumab-lenalidomide-dexamethasone regimen as induction therapy and continuous therapy) are recommended for newly diagnosed multiple myeloma patients who are ineligible for stem-cell transplantation (NDMM). The iCT IRd strategy dominated DRd strategy for NDMM in China by gaining more health benefits and saving costs. The uncertainty of the CUA has limited impact on the cost-effectiveness dominance, supporting the use of iCT IRd strategy as a favorable treatment option."

Clinical • HEOR • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

In Vitro Drug Profiling to Guide Treatment for Relapse/Refractory AML (ASH 2024) - "Significant correlation was observed among drugs of the same classes, for example between inhibitors of PARP (e.g. niraparib-talazoparib, r=0.78, p=1.3e-22), proteasome (e.g. bortezomib-ixazomib, r=0.90, p=4.2e-36), JAK (ruxolitinib-tofacitinib, r=0.91, p=8.3e-35), MEK (cobimetinib-trametinib, p=0.93, p=8.8e-47) and CDK (abemaciclib-palbociclib, p=0.56, p=2.7e-10), confirming that the readout is biologically meaningful. Intriguingly, there were unexpected correlations between specific pairs of drugs of different classes, for instance homoharringtonine (protein translation inhibitor)-abemaciclib (CDK inhibitor) (r=0.65, p=4.3e-17) and between specific gene mutations and drug sensitivity was observed, e.g. sensitivity of CEBPAbZIP mutated samples to PARP inhibitors (p=0.00156), and of AML with inv(16) to MEK inhibitors (p=0.0016)...Drug response to daunorubicin showed good prediction of chemo-resistance in patients who had non-remission after "7+3" (ROC curve AUC..."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3

Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jul 2025 ➔ Apr 2025 | Active, not recruiting ➔ Terminated; Administratively Complete 75%<Participants

Trial completion date • Trial termination • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

The immunomodulatory effects of daratumumab-based therapy on functional high-risk relapse/refractory multiple myeloma (fHRMM) patients enrolled in the MyDRUG trial (AACR 2025) - P1/2 | "Background: The goal of this study is to evaluate the immunomodulatory effects of daratumumab-(anti-CD38)-based therapy on fHRMM patients enrolled in the MMRF sponsored MyDRUG umbrella clinical trial (NCT03732703) over the duration of therapy and to correlate immune changes with patient response. fHRMM who had received 1-3 prior therapies (exposed to at least one proteasome inhibitor and an IMiD) were given a combination of daratumumab (D), ixazomib (I), pomalidomide (P) and dexamethasone (d) (D-IPd) quadruplet therapy. Paired single cell RNA and TCR sequencing of BM T cells from RRMM patients receiving D-IPd quadruplet therapy revealed a selective expansion of clonotypic CD8+ T cells with a clonal replacement of BM exhausted clonotypes by dysfunctional circulating CD8+ T cells in responders over time."

Clinical • Immunomodulating • Hematological Malignancies • Multiple Myeloma • Oncology • CD8 • SDC1

Single cell-based elucidation of molecularly distinct glioblastoma states and drug sensitivity (AACR 2025) - "The top six drugs predicted to target MES and PN subpopulations were tested in acute slices from GBM resections allowing direct characterization of the drug-mediated depletion of subpopulations predicted to be sensitive in adjacent drug vs. vehicle control treated slices [Zhao et al., 2021].Confirming our predictions, we observed statistically significant depletion of the MES and PN compartments by 3 of 3 (Dasatinib, Bexarotene and Prednisone) and 2 of 3 (Givinostat and Ixazomib) OncoTreat-predicted drugs, respectively. Given its high validation rate, this study paves the road and provides significant insight into the future development of combination trials where these drugs may be administered either concomitantly or sequentially. Moreover, the computationally inferred differential activity of subtype-specific MR proteins (CD44, OLIG2, KDM2B, EPHB3, TOP2B and others) was experimentally validated by FACS in cultured patients-derived GBM neurospheres."

Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • EPHB3 • OLIG2

Development of a first-in-class PDIA6/IRE1 modulator for selectively sensitizing cancer cells to ER stress and regulated cell death (AACR 2025) - "NAI003 is a potential first-in-class small-molecule PDIA6/IRE1 modulator that sensitizes cancer cells to ER stress and RCD by selectively overactivating IRE1 signaling. It holds great promise in treating selected cancers either as a single agent or as a combination therapy with marketed anticancer drugs."

Brain Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ATF6 • ERN1 • PDIA6

Altered Immunogenicity of Proteasome Inhibitor-Resistant Myeloma Cells in the 5T33MM Model (IMMUNOLOGY 2025) - "Here, bortezomib (BTZ)-resistant murine 5T33MM (5T33MM-BTZ-R) cells were established by exposure to increasing concentrations of BTZ...Additionally, tumor growth of carfilzomib- and ixazomib-resistant 5T33MM cells was also suppressed in immunocompetent mice...Cytokine analysis showed increased IL-12 and CXCL2/MIP-2 production by 5T33MM-BTZ-R cells. Together, these findings suggest a potential strategy for overcoming MM drug resistance and designing novel immunotherapeutic approaches."

Late-breaking abstract • Hematological Malignancies • Multiple Myeloma • Oncology • IL12A • MIP-2

AlloRelapseMM: Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy (clinicaltrials.gov) - P3 | N=28 | Terminated | Sponsor: Universitätsklinikum Hamburg-Eppendorf | N=482 ➔ 28 | Trial completion date: Mar 2033 ➔ Mar 2025 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2028 ➔ Mar 2025; The reason for the end of recruitment is that the recruitment target could not be achieved despite all efforts and the G-BA (financing party) does not consider a continuation of the AlloRelapseMM study to be expedient.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Establishment and characterization of NCC-PS2-C1: a novel cell line of high-grade pleomorphic spindle cell sarcoma, most consistent with myxofibrosarcoma. (PubMed, Hum Cell) - "Drug screening using NCC-PS2-C1 cells revealed that cobimetinib, crenolanib, and ixazomib were effective against PS. In conclusion, we established NCC-PS2-C1 cells from primary tumors of PS. This cell line is a valuable resource for developing novel chemotherapies."

Journal • Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma

Infection-related adverse events comparison of Bortezomib, Carfilzomib and Ixazomib:A pharmacovigilance study based on FAERS. (PubMed, Expert Opin Drug Saf) - "In real-world pharmacovigilance studies, PIs are associated withinfection-related adverse events, which is crucial for the safe use of PIs inthe treatment of MM. However, further research is needed to validate thehypotheses generated in this study."

Adverse events • Journal • Acute Kidney Injury • Conjunctivitis • Cytomegalovirus Infection • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Pain • Renal Disease

A scientometric study on research characteristics and trends of amyloidosis involving the oral cavity. (PubMed, J Dent Sci) - "The trend of drug aspect, e.g. prednisone, colchicine, corticosteroid, doxorubicin, and vincristine before 2015 has changed to monoclonal antibody, daratumumab, tafamidis, proteasome inhibitor, carfilzomib, ixazomib, patisiran, pomalidomide, diflunisal, and doxycycline. Herein, we highlight the awareness of early diagnosis and improve the access to care for amyloidosis, since oral involvement frequently constitutes the first sign of this disease. This scientometric study elucidated the current scenario and research trends of amyloidosis, underpinning that stomatologists can play roles in providing early recognition and timely diagnosis of amyloidosis when it involved the oral cavity."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Oncology

Study of SubQ Dara With Dose-Attenuated Bortezomib, Lenalidomide, Dexamethasone in Elderly NDMM (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Larysa Sanchez | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ May 2026 | Trial primary completion date: Dec 2024 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Lenalidomide based triplets in relapsed/refractory multiple myeloma: analysis of the Czech Myeloma Group. (PubMed, BMC Cancer) - "This study aims to compare the real-world effectiveness of lenalidomide (LEN)-based triplet therapies, specifically daratumumab (DRD), carfilzomib (KRD), and ixazomib (IRD), in relapsed/refractory multiple myeloma (RRMM).A retrospective registry-based study analyzed 538 RRMM patients undergoing therapy for their first to third relapse. The composition of the cohort is a crucial factor, extending beyond selection criteria. This study highlights the importance of real-world evidence in assessing treatment modalities in clinical settings."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

ADORA2B promotes proliferation and migration in head and neck squamous cell carcinoma and is associated with immune infiltration. (PubMed, BMC Cancer) - "ADORA2B is a key oncogenic driver in HNSC, contributing to tumor proliferation, migration, and an immunosuppressive TME. Its high expression is associated with poor prognosis and reduced immunotherapy efficacy. Targeting ADORA2B may enhance therapeutic outcomes and overcome treatment resistance, highlighting its potential as a diagnostic, prognostic, and therapeutic biomarker."

Biomarker • IO biomarker • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ADORA2B

INFINITE: A Study of Ninlaro in Real World Clinical Practice in China (clinicaltrials.gov) - P=N/A | N=482 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Sep 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2025 ➔ Mar 2026

Real-world evidence • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

I2D IFM2021_03: A Multi-center Open-label Phase 2 Study of Ixazomib, Iberdomide and Dexamethasone in Elderly Patients With Multiple Myeloma at First Relapse." (clinicaltrials.gov) - P2 | N=75 | Active, not recruiting | Sponsor: Nantes University Hospital | Trial completion date: Jan 2027 ➔ Jan 2030 | Trial primary completion date: Jan 2025 ➔ Jan 2030

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=3 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2025 ➔ Jul 2025

Trial completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Safety assessment of proteasome inhibitors real world adverse event analysis from the FAERS database. (PubMed, Sci Rep) - "This study analyzed the AEs reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine the safety profile and differences for the PI drugs bortezomib, carfilzomib, and ixazomib. The PIs were consistent with the early failure model based on time-series analysis of the occurrence of adverse reactions to the drug. The data mined from FAERS generates new AE signals, and further clinical studies are needed to validate these findings."

Adverse events • Journal • Real-world evidence • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Multiple Myeloma • Oncology • Pain

IGM RECOVERY AS A SURROGATE OF EFFECTIVENESS AFTER CAR-T THERAPY FOR RELAPSED AND REFRACTORY MULTIPLE MYELOMA – A SINGLE INSTITUTION RETROSPECTIVE ANALYSIS (EBMT 2025) - "Background: KarMMa-3 trial showed significantly better outcomes in patients with relapsed and refractory multiple myeloma (RRMM) treated with ide-cel than in patients treated with standard of care...As bridging therapy, chemotherapy-based regimen (including VTD-PACE or DCEP) was used for 63% of patients, while others received daratumumab-based, isatuximab-based, carfilzomib-based, or ixazomib-based regimen... Clinical outcomes of our cohort were better than KarMMa-3 study, although follow-up period was not long enough. The reason for better PFS can be due to the administration of conventional chemotherapy as bridging therapy. Better outcome of patients with IgM recovery may be resulted from profound immune reconstitution."

Retrospective data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

TALQUETAMAB IS AN EFFECTIVE THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA WITH PRIOR ALLOGENEIC STEM CELL TRANSPLANTATION: A TWO CASES REPORT (EBMT 2025) - "She was treated with three lines of therapy (including bortezomib, lenalidomide and daratumumab) and was triple class refractory...She was treated with seven lines of therapy, including VAD/DCEP, tandem autoSCT, bortezomib, lenalidomide, bendamustine, and allo-SCT from HLA-identical sibling in 2011...Multiple lines of therapy were administered (including bortezomib, daratumumab, radiotherapy, pomalidomide and ixazomib) with poor efficacy and progression to PCL and extramedullary disease with abdominal bulk in November 2020...At the latest relapse in June 2023 she was treated with talquetamab, complicated during the step-up dose with grade II CRS, managed with tocilizumab... These cases showed promising efficacy of talquetamab in R/R MM patients even in the setting of relapse after alloSCT and secondary PCL with durable responses."

Case report • Clinical • Acute Kidney Injury • Bone Marrow Transplantation • Cardiovascular • Cataract • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Multiple Myeloma • Nephrology • Novel Coronavirus Disease • Oncology • Ophthalmology • Orthopedics • Palliative care • Plasma Cell Leukemia • Primary Biliary Cholangitis • Respiratory Diseases • Septic Shock • Transplantation

Proteasome inhibitors linked to Bowen's disease: Mechanistic insights from integrative bioinformatics guided disproportionality analysis of FAERS database (Sarcoma-RC 2025) - "Results FAERS data showed Reporting Odds Ratios (ROR) for BD of 9.187, 6.046, and 6.899 for Bortezomib, Ixazomib, and Carfilzomib, with Proportional Reporting Ratios (PRR) of 9.183, 6.044, and 6.897. Legal entity responsible for the study The authors. Funding Has not received any funding."

Bowens Disease • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • BRAF • CCND1 • JAK2 • STAT3

Trial of Ixazomib for Kaposi Sarcoma (clinicaltrials.gov) - P2 | N=41 | Recruiting | Sponsor: AIDS Malignancy Consortium | Trial completion date: May 2026 ➔ Mar 2029 | Trial primary completion date: May 2025 ➔ Mar 2029

Trial completion date • Trial primary completion date • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor

Establishment and characterization of NCC-dCS2-C1: a novel patient-derived cell line of dedifferentiated chondrosarcoma. (PubMed, Hum Cell) - "High-throughput screening of 221 anticancer drugs using NCC-dCS2-C1 identified three candidates, ixazomib, pazopanib, and ponatinib, that demonstrated low IC50 values, indicating their potential efficacy in treating dCS. We conclude that NCC-dCS2-C1 is a valuable tool for preclinical and basic research on dCS."

Journal • Preclinical • Oncology • Sarcoma • Solid Tumor • IDH1

Cost-effectiveness analysis of combination therapies involving novel agents for first/second-relapse patients with multiple myeloma: a Markov model approach with calibration techniques. (PubMed, Health Econ Rev) - "Although this study did not fully account for the heterogeneity of subsequent treatment regimens among first/second-relapse MM patients, it highlights that the substantial financial burden associated with combination therapies involving novel agents poses a significant challenge in justifying their economic value."

Clinical • HEOR • Journal • Hematological Malignancies • Multiple Myeloma • Oncology