Ninlaro (ixazomib) / Takeda - LARVOL DELTA

Single-cell transcriptomic insights into tumor and immune dynamics driving resistance to ixazomib combined with gemcitabine and doxorubicin in SMARCB1-deficient renal medullary carcinoma (AACR 2026) - "Integrative cell-cell communication analysis highlighted stromal-immune signaling through BMP4/5 and WNT4/6 as a hallmark of resistant tumors, whereas BMP6 expression associated with dendritic-cell activation and favorable immune remodeling. Together, these findings define molecular and cellular programs underlying therapeutic response in RMC and nominate actionable stress-adaptation and stromal-immune circuits as potential targets for future biomarker-guided combination strategies."

Genito-urinary Cancer • Kidney Cancer • Kidney Medullary Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor • BAG4 • BMP4 • BMP6 • CAFs • CD4 • CD8 • CDK1 • S100A8 • SMARCB1 • UBE4B

Cysteine accumulation as a driver of resistance to bortezomib (AACR 2026) - "We identified cells to be more resistant to boronic-acid proteasome inhibitors in high cysteine conditions (Bortezomib (Btz) and Ixazomib (Ixa)), but not to the epoxyketone-containing proteasome inhibitor Carfilzomib (Cfz)...Conversely, when we decrease intracellular cysteine levels by co-treating with erastin, an inhibitor of SLC7A11, we measured that cells become more sensitive to Btz and Ixa...We did not measure a difference in proteasome function in carfilzomib-treated cells in high cysteine, once again implying a unique direct interaction between boronic acid-containing inhibitors and cysteine.In summary, we uncovered a novel mechanism of resistance to boronic acid-containing proteasome inhibitors with straightforward possibilities to reverse resistance. This work has clinical implications for cancer treatment, especially those with ATF4 or NRF2 stabilization which both drive cysteine accumulation in a SLC7A11-dependent manner."

Oncology • ATF4 • SLC7A11

NOVEL THERAPIES FOR RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA POST BRUTON'S TYROSINE KINASE INHIBITOR: A TARGETED LITERATURE REVIEW (ISPOR 2026) - "Five ongoing studies without outcomes reported are evaluating ixazomib, odronextamab, and rocbrutinib...Drugs evaluated included antibody-drug conjugates (ADCs) (zilovertamab, polatuzumab + obinutuzumab), bispecific antibodies (BsAbs) (mosunetuzumab-based, glofitamab), noncovalent BTKi (ncBTKi) (pirtobrutinib), chimeric antigen receptor T-cell (CAR-T) (brexucabtagene, lisocabtagene, tisagenlecleucel), ViPOR regimen (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide), proteasome inhibitor (PI) (carfilzomib)... Preliminary data indicate promising but heterogenous results within drug classes. Interpretation is limited by small sample sizes and differences in study design, underscoring the need for further investigation in this area of high unmet need."

Review • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma

A Randomized Phase 2 Study of Daratumumab, Lenalidomide, Ixazomib, and Dexamethasone in Transplant-Ineligible/Deferred Patients with Newly Diagnosed Multiple Myeloma: Alliance Foundation Trial 41 (IMS 2025) - P2 | "Dara-RId offers a regimen that has the efficacy of a 4 drug combination with the convenience of oral ixazomib and minimizes the risk of peripheral neuropathy for older, transplant ineligible NDMM. There is ongoing follow up to determine the benefit of maintenance with dara RI v. R alone. Support: AFT, Celgene, Janssen, Takeda"

Clinical • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia • Transplantation

Final Results of randomized Phase II study of daratumumab, ixazomib, and dexamethasone (DId, ARM A) vs daratumumab, bortezomib and dexamethasone (DVd) followed by daratumumab, did (Arm B) in newly diagnosed multiple myeloma (DeRIVE) study (ASH 2025) - "This is one of the first studies showing the safety and efficacy of non-IMID baseddaratumumab-combination induction therapies with in-class transition of bortezomib to ixazomib (ArmB) yielding higher response rates post-induction and post-transplant without compromising on thesafety. This translated to PFS and OS benefit as well with no survival events for Arm B with more than 60month follow up."

Clinical • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Prostate Cancer • Solid Tumor

Novel covalent ligand modulates proteasome activity and assembly in colorectal cancer (ESMO-TAT 2026) - "However, clinically approved proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, have shown limited efficacy in treating solid tumours like CRC. Our study highlights the substantial potential of a 19S regulatory particle as a novel druggable target in CRC and introduces a novel class of proteasome inhibitor with a mechanism of action distinct from that of clinically used proteasome inhibitors. This offers a unique mechanism of action that disrupts proteasome activity and assembly."

Colorectal Cancer • Oncology • Solid Tumor

Frail subgroups determine heterogeneous outcomes in older patients with NDMM - long-term follow-up of the HOVON 143 trial. (PubMed, Blood Adv) - P2 | "Patients who were classified as frail according to the IMWG-FI, were treated with nine induction cycles of ixazomib, daratumumab and low dose dexamethasone, followed by maintenance therapy until progression for a maximum of 2 years. These findings highlight the need for a more precise frailty definition to identify patients at highest risk of early mortality. EudraCT number: 2016-002600-90."

Heterogeneity • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

KarMMa-3: Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=381 | Not yet recruiting | Sponsor: Celgene

New P3 trial • Multiple Myeloma

KarMMa-3: Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=381 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

KarMMa-3: Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=381 | Recruiting | Sponsor: Celgene | Trial completion date: Jun 2025 ➔ Nov 2025 | Trial primary completion date: Jun 2025 ➔ May 2022

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

SYSTEMATIC LITERATURE REVIEW OF REAL-WORLD EVIDENCE IN RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (ISPOR 2026) - "OBJECTIVES: This systematic literature review aimed to evaluate the comparative effectiveness, health-related quality of life (HRQL), treatment preferences, and economic burden associated with lenalidomide plus dexamethasone (Rd)-based triplet regimens in relapsed and/or refractory multiple myeloma (RRMM). This review followed the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration: CRD420251136008)...Across unique studies, carfilzomib-Rd (KRd) was evaluated most frequently (n = 17), followed by ixazomib-Rd (IRd) and daratumumab-Rd (DRd) (n = 13 each), bortezomib-Rd (VRd; n = 9), and elotuzumab-Rd (ERd; n = 5)... Real-world evidence indicates that IRd provides effectiveness comparable to other Rd-based triplet regimens while offering lower healthcare costs and fewer outpatient visits, supporting its value as a treatment option in routine practice for RRMM. As new comparative evidence..."

Clinical • HEOR • Real-world • Real-world evidence • Review • Hematological Malignancies • Multiple Myeloma

KarMMa-3: Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=381 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ Apr 2027 | Trial primary completion date: Sep 2026 ➔ Apr 2027

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

DISPROPORTIONALITY ANALYSIS AND MULTIMODAL GENETIC ASSESSMENT OF PAPILLEDEMA ASSOCIATED WITH PROTEASOME INHIBITORS (ISPOR 2026) - "Key compounds and hub targets were prioritised for molecular docking using Chimera and AutoDock Vina, while functional enrichment analyses (GO and KEGG) were conducted using Metascape and Cytoscape. A total of 1,962 signals were identified, of which 58 papilledema cases were associated with Bortezomib (n=35), Carfilzomib (n=10), and Ixazomib (n=13). This study identified a potential association between PI and papilledema through disproportionality analysis and comprehensive genetic assessment. Although further clinical research is crucial to verify this corroboration, healthcare providers are opined to be vigilant."

Hematological Malignancies • Lymphoma • Multiple Myeloma • Ophthalmology • PIK3CA

Real-world efficacy and tolerability of ixazomib-based combination therapies in advanced multiple myeloma and other plasma cell neoplasms. (PubMed, Ther Adv Hematol) - "Grade ⩾3 hematologic adverse events occurred in 15.1% patients, while the most common non-hematologic adverse events were fatigue (5.6%) and peripheral neuropathy (26.2%), with the majority classified as grade 1-2. Altogether, ixazomib regimens are potent in RRMM but are less effective in heavily pretreated patients and those with renal impairment, suggesting earlier use may yield greater benefits."

Journal • Real-world evidence • Fatigue • Hematological Malignancies • Multiple Myeloma • Pain • Plasmacytoma • Renal Disease

INFINITE: A Study of Ninlaro in Real World Clinical Practice in China (clinicaltrials.gov) - P=N/A | N=482 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

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

Ixazomib triggers autophagic degradation of MUC5AC/integrin-β4 and inhibits non-small cell lung cancer progression. (PubMed, Cancer Lett) - "IXZ effectively inhibited LUAD tumor growth and may overcome platinum resistance. These findings warrant further investigation into the clinical role of IXZ alone or in combination with CBP or other chemotherapies in patients with LUAD."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ATG5 • BAG3 • MUC5AC • UCHL1

Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Raija Silvennoinen | Initiation date: Dec 2017 ➔ Mar 2018

Minimal residual disease • Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Raija Silvennoinen | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2018 ➔ May 2018

Enrollment open • Minimal residual disease • Trial initiation date • Multiple Myeloma • Transplantation

Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Raija Silvennoinen

Minimal residual disease • New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Raija Silvennoinen | Recruiting ➔ Active, not recruiting

Enrollment closed • Minimal residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Cardiovascular Adverse Events Associated With Carfilzomib, Bortezomib, and Ixazomib: A Disproportionality Analysis Using the Japanese Adverse Drug Event Report Database With Anticancer Agents as the Reference Group. (PubMed, In Vivo) - "These findings highlight the potential influence of patient demographics on CVAE risk and support tailored monitoring strategies for patients receiving PIs, particularly older adult and male patients."

Adverse events • Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Oncology • Venous Thromboembolism

FLT3-SYK inhibitor and Ixazomib combination impact HOXA and oxidative stress control by β-catenin, SQSTM1 and NRF2 in AML. (PubMed, NPJ Precis Oncol) - P1/2 | "Dual targeting of FLT3/SYK (TAK-659) and the proteasome (Ixazomib) showed strong synergy across genetically defined AML subsets, irrespective of FLT3 mutant status. These findings define a therapeutically targetable axis linking FLT3/SYK/β-catenin signaling to stress adaptation, provide a mechanistic basis for combinatorial targeting in high-risk AML. Trial registration: NCT04079738, Date of registration 03 September 2019."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • Transplantation • CTNNB1 • FLT3 • HOXA9 • JUN • PTPRC • SQSTM1 • SYK • TET2

"Et tu, Brute?" -A Case of Ixazomib-Induced Cancer Therapy-Related Cardiac Dysfunction. (PubMed, Intern Med) - "Despite the discontinuation of ixazomib and continued administration of guideline-directed medical therapy, his LVEF has not recovered to date. We herein report a rare case of ixazomib-induced irreversible CTRCD."

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

Is IMWG frailty-score-adjusted dosing the right approach to improve toxicity and outcomes in FRAIL patients? Results from the UK-MRA FiTNEss trial in newly diagnosed myeloma patients ineligible for ASCT. (ASH 2025) - P3 | "The primary objectives are to compare standard and frailty-score adapted (FA) induction therapy with an oral PI/IMiD combination (ixazomib, lenalidomide,dexamethasone, IRD) for 12 cycles and, after a second randomisation (R2), to compare maintenance R toIR. Our datasuggest the recently approved anti-CD38/IMiD/PI combinations should be used cautiously in FRAILpatients even with FA dosing strategies. Future studies should explore other approaches such astreatment switching for FRAIL patients with a suboptimal response."

Clinical • Hematological Malignancies • Infectious Disease • Multiple Myeloma

A Phase 1 Study of Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis. (PubMed, Am J Hematol) - No abstract available

Journal • P1 data • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology