This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-protein data from two phase III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs. in combination with daratumumab. Three M-protein dynamic features from the longitudinal M-protein data were evaluated up to different time cutoffs (1, 2, 3, and 6 months). The abilities of early M-protein dynamic measurements to predict the PFS were evaluated using Cox proportional hazards survival models. Both univariate and multivariable analyses suggest that maximum reduction of M-protein (i.e., depth of response) was the most predictive of PFS. Despite the statistical significance, the baseline covariates provided very limited predictive value regarding the treatment effect of daratumumab. However, M-protein dynamic features obtained within the first 2 months reasonably predicted PFS and the associated treatment effect of daratumumab. Specifically, the areas under the time-varying receiver operating characteristic curves for the model with the first 2 months of M-protein dynamic data were ~ 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within the first 2 months can provide a prospective and reasonable prediction of future long-term clinical benefit for patients with MM.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719372 | PMC |
| http://dx.doi.org/10.1111/cts.12836 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Group a remains viable inside fibrin clots and gains access to human plasminogen for subsequent fibrinolysis and dissemination.
Microbiol Spectr
January 2025
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
Unlabelled: Group A (GAS) is a major human pathogen that causes several invasive diseases including necrotizing fasciitis. The host coagulation cascade initiates fibrin clots to sequester bacteria to prevent dissemination into deeper tissues. GAS, especially skin-tropic bacterial strains, utilize specific virulence factors, plasminogen binding M-protein (PAM) and streptokinase (SK), to manipulate hemostasis and activate plasminogen to cause fibrinolysis and fibrin clot escape.
View Article and Find Full Text PDFThe E3 ligase RAD18-mediated ubiquitination of henipavirus matrix protein promotes its nuclear-cytoplasmic trafficking and viral egress.
Emerg Microbes Infect
December 2025
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
The nuclear-cytoplasmic trafficking of matrix proteins (M) is essential for henipavirus budding, with M protein ubiquitination playing a pivotal role in this dynamic process. Despite its importance, the intricacies of the M ubiquitination cascade have remained elusive. In this study, we elucidate a novel mechanism by which Nipah virus (NiV), a highly pathogenic henipavirus, utilizes a ubiquitination complex involving the E2 ubiquitin-conjugating enzyme RAD6A and the E3 ubiquitin ligase RAD18 to ubiquitinate the virus's M protein, thereby facilitating its nuclear-cytoplasmic trafficking.
View Article and Find Full Text PDFDirect lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly.
bioRxiv
November 2024
Borch Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, Indiana 47907.
Article Synopsis
- M is a crucial structural protein in coronaviruses, specifically SARS-CoV-2, playing a key role in forming infectious virus particles and existing in two conformational states.
- The study identifies a specific interaction between the M protein and a type of lipid (ceramide-1-phosphate) that influences M's structure and its ability to facilitate virus assembly.
- Disrupting this lipid-protein interaction impacts M's localization and its interactions with other viral proteins, ultimately hindering the virus's ability to enter host cells.
SARS-CoV-2 N protein coordinates viral particle assembly through multiple domains.
J Virol
November 2024
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
Increasing evidence suggests that mutations in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may enhance viral replication by modulating the assembly process. However, the mechanisms governing the selective packaging of viral genomic RNA by the N protein, along with the assembly and budding processes, remain poorly understood. Utilizing a virus-like particles (VLPs) system, we have identified that the C-terminal domain (CTD) of the N protein is essential for its interaction with the membrane (M) protein during budding, crucial for binding and packaging genomic RNA.
View Article and Find Full Text PDFModeling serum M-protein response for early detection of biochemical relapse in myeloma patients treated with bortezomib, lenalidomide and dexamethasone.
CPT Pharmacometrics Syst Pharmacol
December 2024
Laboratory of Pharmacometrics and Systems Pharmacology, Keio Frontier Research and Education Collaboration Square (K-FRECS) at Tonomachi, Keio University, Kanagawa, Japan.
Multiple myeloma (MM) treatment guidelines recommend waiting for formal progression criteria (FPC) to be met before proceeding to the next line of therapy. As predicting progression may allow early switching to next-line therapy while the disease burden is relatively low, we evaluated the predictive accuracy of a mathematical model to anticipate relapse 180 days before the FPC is met. A subset of 470/1143 patients from the IA16 dataset who were initially treated with VRd (Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone) in the CoMMpass study (NCT01454297) were randomly split 2:1 into training and testing sets.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!