bortezomib

When combined with the frontline MM chemotherapy agent bortezomib, SSTNIV conferred the greatest survival benefit, substantially reducing MM cells in BM, alleviating extramedullary disease, and restoring hematopoiesis. Furthermore, human BM microarray analysis using proximity ligation assay confirmed that Sdc1 forms complexes with receptor tyrosine kinases and integrins in human MM tumors targeted by SSTNIV, but not in normal BM. These findings highlight SSTNIV's potent anti-myeloma activity and support its potential as a promising therapeutic strategy for advanced and relapsed/refractory MM.

P2, N=30, Active, not recruiting, PETHEMA Foundation | Trial primary completion date: Mar 2025 --> Mar 2026

P2, N=160, Active, not recruiting, University of Arkansas | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

This study investigated the associations of sFLC κ, λ and the κ/λ ratio with clinical features, cytogenetic abnormalities, prognosis and response to the VRd regimen (bortezomib, lenalidomide, dexamethasone) in newly diagnosed MM (NDMM) patients, aiming to optimize risk stratification. In conclusion, abnormal sFLC κ is a potential marker of poor prognosis and suboptimal response to VRd therapy in NDMM. Integrating sFLC κ with the R-ISS improves risk stratification, providing new evidence for clinical application of this biomarker.

P2/3, N=153, Not yet recruiting, AstraZeneca AB

P4, N=141, Terminated, Takeda | Trial completion date: Nov 2026 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2026 --> Mar 2026; All participants on the study have concluded treatment, core study activities are complete, and the scientific goals of the study have been met.

P3, N=475, Active, not recruiting, Sanofi | Trial primary completion date: Apr 2026 --> Apr 2027

P1/2, N=300, Active, not recruiting, Karyopharm Therapeutics Inc | Recruiting --> Active, not recruiting

This intervention markedly reduces intracellular copper overload, eliciting a dual regulatory effect: on one hand, the decreased copper concentration directly inhibits the oligomerization of DLAT; on the other hand, it effectively protects the iron-sulfur cluster protein FDX1 from damage. This study aims to systematically elucidate the molecular mechanisms underlying BIPN and to evaluate the therapeutic potential of EGCG in alleviating BIPN, offering a novel therapeutic strategy for the prevention and treatment of BIPN.

These findings should be considered exploratory given the sample size and require confirmation in larger cohorts. Nonetheless, they suggest a potential role for pharmacogenomics in supporting future approaches to treatment personalization.

A secondary objective was to assess whether mRNA expression levels of the endoplasmic reticulum (ER) stress sensors X-box-binding protein 1 (uXBP1) and activating transcription factor 6 (ATF6), and the chaperone-mediated autophagy marker Lysosomal-Associated Membrane Protein 2 (LAMP2A) by droplet digital PCR (ddPCR), were associated with resistance to the second-generation proteasome inhibitor (PI) carfilzomib (Cfz)...Samples were obtained as part of standard clinical care and/or during treatment with Bortezomib (Btz) or Cfz...Cfz adaptation was associated with reduced levels of uXBP1 and LAMP2A mRNA in MM cell lines. Future prospective studies evaluating the clinical utility of ER stress and chaperone-mediated autophagy associated transcripts in CPCs as predictors of resistance to PI are warranted.

P2/3, N=38, Not yet recruiting, AstraZeneca AB