Ninlaro (ixazomib) / Takeda - LARVOL DELTA

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - P2 | "New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax...CXCR4 antagonists such as plerixafor or ulocuplumab can sensitize CXCR4Mut-expressing WM cells to ibrutinib [22-24]...6 BTK Mutations BTKCys481 is the binding site for covalent BTK inhibitors (cBTK-i), including ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib and tirabrutinib...For symptomatic treatment-naïve patients, chemoimmunotherapy with bendamustine and rituximab (Benda-R), dexamethasone, rituximab, and cyclophosphamide (DRC), as well as cBTK-i can be considered...Additional options in second or later relapse include re-use of chemotherapy if a response lasted for > 3 years, alternative chemoimmunotherapy, nucleoside analogs, or everolimus [38]...Zanubrutinib in combination with ixazomib and dexamethasone (ZID) is being investigated in a study in China (NCT04463953) and has shown high levels of response activity and good..."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCLAF1 • CXCL12 • FOXO3 • IL10 • IL6 • IRAK4 • MYD88 • PLCG2 • SYK • TNFAIP3 • TRAF3IP2

Isolated relapse of multiple myeloma in the central nervous system post autologous hematopoietic stem cell transplantation: a case report and literature review. (PubMed, Front Oncol) - "The patient responded better to combination therapy involving doxorubicin liposomes and a triple intrathecal injection of dexamethasone plus methotrexate plus cytarabine. However, regimens based on the daratumumab, pomalidomide, ixazomib, and selinexor failed to achieve sustained remission in this patient. Seventeen months after experiencing CNS relapse, the patient died because of disease progression. Currently, there is no standard treatment strategy for CNS myeloma and the overall prognosis is still poor."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

IPD regimen effect on the levels of VEGF and IL-6 in elderly patients with recurrent multiple myeloma. (PubMed, Indian J Cancer) - "IPD regimen for relapsed elderly multiple myeloma has the characteristics of improving clinical efficacy and inhibiting VEGF and IL-6, TNF-α, concentrations increase. However, compared with TD therapy, IPD regimen has similar effects on the risk and time of progression."

Clinical • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • IL6 • TNFA

Engineered Flagellin Biomaterial as a Pattern Recognition Receptor Signal Activating Immunostimulants and Controlled Release of Boronated Anti-Cancer Drugs. (PubMed, ACS Appl Bio Mater) - "This modification facilitated the self-assembly of the flagellin derivative and enabled efficient covalent conjugation with the boron-based anticancer drug Ixazomib, allowing for targeted drug release under physiological conditions...It resulted in a 70% reduction in 3D tumor spheroid viability and an 80% inhibition of 20S proteasome activity. This dual-action approach of selective immune activation and precise drug delivery highlights the potential of flagellin derivative-based therapeutics for glioblastoma and other TLR5-expressing tumors."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MYD88

Design, Synthesis, and Evaluation of Aza-Peptide Michael Acceptors as Human 20S Proteasome Inhibitors: Extension to the Prime Site. (PubMed, ACS Omega) - "Current FDA-approved proteasome inhibitor (PI) drugs, such as bortezomib, carfilzomib, and ixazomib, have significantly improved the treatment of multiple myeloma (MM) over the past 20 years. Our top compound, Mp-HPh-Leu-Phe-ALeu-CHCH-CONHBn, is a submicromolar inhibitor of the catalytic ß5 subunit. The selectivity of these inhibitors over other classes of proteases makes them suitable for further development as candidate therapeutic agents to potentially treat multiple myeloma, neurodegenerative disorders, and infectious diseases."

Journal • CNS Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Targeted Protein Degradation

A Novel Chemotherapy Combination to Enhance Proteotoxic Cell Death in Hepatocellular Carcinoma Experimental Models Without Killing Non-Cancer Cells. (PubMed, Int J Mol Sci) - "In the Hep3B xenograft model, rencofilstat + ixazomib significantly inhibited tumor volumes/weights without general toxicity. We conclude that rencofilstat + ixazomib amplified proteotoxic stress in hepatocellular carcinoma past a threshold pro-survival pathways could not tolerate, whereas non-cancer cells were less affected."

Journal • Hematological Malignancies • Hepatocellular Cancer • Multiple Myeloma • Oncology • Solid Tumor • Targeted Protein Degradation

Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGvHD biomarkers. (PubMed, Blood Adv) - P1/2 | "It is possible to identify biological patterns by flow cytometry to predict the risk of cGvHD. ClinicalTrials.gov Identifier: NCT03225417."

Biomarker • Journal • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation • STAT3

MC1382: Ixazomib With Cyclophosphamide and Dexamethasone in Patients With Previously Untreated Symptomatic Multiple Myeloma or Light Chain Amyloidosis (clinicaltrials.gov) - P1/2 | N=87 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

Trial completion • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology

Pharmacovigilance and signal detection of adverse drug events associated with proteasome inhibitors in multiple myeloma: a real-world analysis using the FAERS database. (PubMed, Hematology) - "Proteasome inhibitors (PIs) such as Bortezomib, Carfilzomib, and Ixazomib have significantly improved outcomes in multiple myeloma (MM), but their real-world safety profiles require further exploration. This study highlights both known and newly detected ADEs linked to PIs, emphasizing the importance of early-phase monitoring and ongoing pharmacovigilance. The findings provide crucial real-world evidence for clinical risk management and future label updates."

Adverse events • Journal • Real-world evidence • Cardiovascular • CNS Disorders • Cognitive Disorders • Developmental Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Small nuclear ribonucleoprotein polypeptide B2 regulated by SNHG4/miR-204-5p axis inhibits ferroptosis to aggravate the progression of hepatocellular carcinoma. (PubMed, Discov Oncol) - "SNRPB2, a spliceosome component, is well known to participate in the pre-splicing of mRNA and enhance the apoptosis induction impact of ixazomib on multiple myeloma cells. Finally, SNRPB2 deficiency increases the sorafenib sensitivity of HCC cells. Conclusively, our study uncovers the previously unknown role of SNRPB2 in HCC, reveals the related ceRNA regulatory axis of SNRPB2, and identifies a novel ferroptosis regulating protein, suggesting SNRPB2 appears to be a promising target for HCC therapy."

Journal • Hematological Malignancies • Hepatocellular Cancer • Multiple Myeloma • Oncology • Solid Tumor • MIR204

Real-World Comparison of Carfilzomib, Lenalidomide, and Dexamethasone Versus Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma: KMM2004 Study. (PubMed, Clin Lymphoma Myeloma Leuk) - "Comparing the two treatments in the real-world revealed inconsistent outcomes from the predictions based on RCTs. The KRd showed an advantage in the depth of response, while the IRd showed an advantage in the duration of the response. The findings will be helpful in choosing the best strategies of treatment for patients with RRMM."

Journal • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma. (PubMed, Discov Oncol) - "Our research results indicate that the autophagy-related exosome genes PTK6, ITGA3 and ITGB4 are independent risk factors for PC and may promote PC development and invasion by promoting cell-cell adhesion and cell-matrix adhesion, inhibiting tumor cell autophagy, promoting nerve infiltration, reducing CD8 + T-cell content, and increasing M0 and M2 macrophage content. Drug susceptibility analysis showed that crizotinib, tamoxifen, ixazomib, and carboplatin had inhibitory effects on ITGA3, ITGB4, and PTK6."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • ITGA3 • ITGB4 • PTK6

A Study of NINLARO® in Chinese Adults With Multiple Myeloma (clinicaltrials.gov) - P=N/A | N=160 | Recruiting | Sponsor: Takeda | Trial completion date: Jun 2027 ➔ Dec 2027 | Trial primary completion date: Jun 2027 ➔ Dec 2027

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

Decoding Drug Efficacy in Glioblastoma: Identifying Pan-Effective Therapeutics Against Tumor-Initiating Cells to Counteract Heterogeneity (EACR 2025) - "Standard treatment includes surgical resection followed by radiotherapy and temozolomide chemotherapy, yet 80–90% of patients relapse...From this subset, we prioritized three candidates: Homoharringtonine, a protein synthesis inhibitor; Ixazomib Citrate, a proteasome inhibitor; and Panobinostat, a histone deacetylase inhibitor... These results highlight our TICs panel as a valuable screening platform for real-time therapy monitoring and for identifying promising TIC-targeting drugs for GBM treatment. Future work will explore resistance mechanisms using single-cell transcriptomic and epigenomic profiling, and develop rational combination therapies."

Clinical • Heterogeneity • Late-breaking abstract • Brain Cancer • Glioblastoma • Movement Disorders • Oncology • Solid Tumor

Integrative Pharmacogenomics in RCC Tumoroids Uncovers Biomarker-Driven Combination Therapies (EACR 2025) - "Scaffold-free tumoroids faithfully recapitulate interpatient heterogeneity in RCC, serving as robust platforms for drug discovery. Our pharmacogenomic framework identifies actionable therapeutic vulnerabilities and predictive biomarkers, providing a rationale for personalized combination therapies."

Biomarker • Combination therapy • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • IR

Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement (clinicaltrials.gov) - P2 | N=70 | Completed | Sponsor: Emory University | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Successful treatment with carfilzomib and dexamethasone for relapsed/refractory POEMS syndrome: a case report and review of literature. (PubMed, Front Oncol) - "After multiple lines of treatment, including bortezomib, cyclophosphamide, and dexamethasone (VCD), ixazomib, and daratumumab along with dexamethasone (DD), her clinical and laboratory features, and cardiovascular system continued to deteriorate. We report on the first case of relapsed/refractory POEMS syndrome who received carfilzomib and dexamethasone, and achieved very good remission. Carfilzomib may be a safe and effective treatment option for patients with relapsed/refractory POEMS syndrome."

Journal • Anorexia • Cardiovascular • Fatigue • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Plasmacytoma • Rare Diseases • Rheumatology • Transplantation

Lenalidomide, ixazomib, or daratumumab maintenance therapy in multiple myeloma. (PubMed, Blood Neoplasia) - "Lenalidomide was associated with second malignancies, ixazomib with thrombocytopenia, and daratumumab with pneumonia. We propose that lenalidomide remains the maintenance therapy of choice for NDMM."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation

Case Report: BCMA-targeting CAR T-cell therapy induces complete and durable remission in relapsed extramedullary plasmablastic multiple myeloma. (PubMed, Front Immunol) - "Following induction chemotherapy with bortezomib, doxorubicin and dexamethasone (VAD), and subsequent consolidation therapy with ixazomib, lenalidomide, and dexamethasone, the disease progressed, manifesting as a plasmoblastic tumor in the right pelvic cavity. After two cycles of carfezomib, daratumumab, cyclophosphamide, cisplatin, etoposide and dexamethasone (KD-DECP), the patient achieved partial response...BCMA CAR-T cell accompanied with bridging radiotherapy and pomalidomide as maintenance therapy provided a promising therapy treatment for PBM, which is more aggressive and with shorter survival. Further studies are demanded to assess the efficiency and long-term benefits for this challenging subtype."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Treatment Patterns, Goals, and Decision-Making Criteria for Second- and Third-Line Therapies for Multiple Myeloma in Germany. (PubMed, Adv Ther) - "The results suggest that in the absence of a single standard of care for RRMM, prescribers made patient-centred choices of regimens with efficacy as the main goal of therapy."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Ixazomib and Pevonedistat in Treating Patients With Multiple Myeloma That Has Come Back or Does Not Respond to Treatment (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: National Cancer Institute (NCI) | Phase classification: P1b ➔ P1

Phase classification • Hematological Malignancies • Multiple Myeloma • Oncology

Pharmacoeconomic evaluation of carfilzomib versus ixazomib for the treatment of relapsed and refractory multiple myeloma. (PubMed, Future Sci OA) - "This study assesses the cost-effectiveness of carfilzomib plus lenalidomide and dexamethasone (KRd) versus ixazomib plus lenalidomide and dexamethasone for relapsed and refractory multiple myeloma (RRMM) in China. At a $40,023.27 willingness-to-pay (WTP) threshold, the carfilzomib combination has a 100% probability of being cost-effective. The study shows that, based on evidence from indirect comparisons, KRd is a cost-effective treatment option for RRMM patients in China."

HEOR • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

THE IRD REGIMEN CONTINUED AFTER EFFECTIVE INDUCTION WITH DRD FOR TRANSPLANT-INELIGIBLE PATIENTS WITH MULTIPLE MYELOMA: A MULTI-CENTER PROSPECTIVE STUDY IN CHINA (EHA 2025) - P4 | "Background: The continuous treatment regimen of DRd (daratumumab/lenalidomide/dexamethasone) has been proven to significantly improve the prognosis of newly diagnosed multiple myeloma(NDMM)patients...Aims: The primary research objective is to observe the 2-year progression-free survival (PFS) in transplant-ineligible patients with NDMM after sequential IRd(ixazomib/lenalidomide/dexamethasone)regimen treatment following DRd regimen induction therapy... In conclusion, outcomes of the study indicate that sequential IRd regimen treatment following DRd regimen induction therapy in transplant-ineligible patients with NDMM can further deepen the depth of remission and safety data suggest IRd is generally well tolerated."

Clinical • Infectious Disease • Multiple Myeloma • Pain • Transplantation

CLINICAL OUTCOMES OF RELAPSED OR REFRACTORY MULTIPLE MYELOMA OVERALL AND AMONG LENALIDOMIDE-REFRACTORY PATIENTS IN EAST ASIA: A TARGETED LITERATURE REVIEW (EHA 2025) - "Treatment regimens: thalidomide + dexamethasone (DEX; South Korea); ixazomib (IXA) + LEN + DEX (Japan); daratumumab + DEX + cyclophosphamide + etoposide + cisplatin (CN); IXA + clarithromycin + LEN + DEX (CN).Among LEN-refractory pts in EA: median PFS 5.5-11.9mo, median OS 9.2-12mo, ORR 20-65% (DOR not reported). In CN, a retrospective review of 17 LEN+bortezomib-refractory pts reported: median PFS 8mo, median OS 12mo, ORR 65%; another study with 42.9% (12/28) of LEN-refractory pts reported: median PFS 11.7mo, ORR 50% (OS not reported)... RRMM clinical outcomes are poor in EA under the existing treatments available, with studies generally reporting OS <2yrs overall and <1yr in LEN-refractory pts. Data across EA were highly variable, likely due to differences in line of treatment at time of study, differing efficacy/accessibility of RRMM treatment options, and small study sizes, especially in LEN-refractory pts. LEN-refractory pt data were scarce and inconsistently..."

Clinical • Clinical data • Review • Hematological Malignancies • Multiple Myeloma • Oncology