Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis.

ABSTRACT: (1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.

SUBMITTER: Fujimoto Y

PROVIDER: S-EPMC8616141 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma.

Project description:Multiple myeloma (MM) remains incurable despite the number of novel therapies that have become available in recent years. Occasionally, a patient with MM will develop an amyloid light-chain (AL) amyloidosis with organ dysfunction. Chimeric antigen receptor T-cell (CART) therapy has become a promising approach in treating hematological malignancies. Our institution has developed a second-generation B-cell maturation antigen (BCMA)-CART which is currently being tested in a clinical trial for relapsed/refractory MM.We present the first reported case, to our knowledge, of a patient with AL amyloidosis and renal involvement in the course of an MM, successfully treated with CART therapy targeting BCMA. The patient received a fractioned dose of 3×106/kg BCMA-CARTs after lymphodepletion. At 3 months from infusion, the patient had already obtained a deep hematological response with negative measurable residual disease by flow cytometry in the bone marrow. After 12 months, the patient remains in hematological stringent complete remission and has achieved an organ renal response with a decrease of 70% of proteinuria.This case suggests that concomitant AL amyloidosis in the setting of MM can benefit from CART therapy, even in patients in which predominant symptoms at the time of treating are caused by AL amyloidosis.

| S-EPMC8655576 | biostudies-literature

Cytogenetic intraclonal heterogeneity of plasma cell dyscrasia in AL amyloidosis as compared with multiple myeloma.

Project description:Analysis of intraclonal heterogeneity has yielded insights into the clonal evolution of hematologic malignancies. We compared the clonal and subclonal compositions of the underlying plasma cell dyscrasia in 544 systemic light chain amyloidosis (PC-AL) patients with 519 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or symptomatic MM; ie, PC-non-AL patients). Using interphase fluorescence in situ hybridization, subclones were stringently defined as clone size below two thirds of the largest clone and an absolute difference of ≥30%. Subclones were found less frequently in the PC-AL group, at 199 (36.6%) of 544 as compared with 267 (51.4%) of 519 in the PC-non-AL group (P < .001), and were not associated with the stage of plasma cell dyscrasia in either entity. In both groups, translocation t(11;14), other immunoglobulin heavy chain translocations, and hyperdiploidy were typically found as main clones, whereas gain of 1q21 and deletions of 8p21, 13q14, and 17p13 were frequently found as subclones. There were no shifts in the subclone/main clone ratio depending on the MGUS, SMM, or MM stage of plasma cell dyscrasia. In multivariate analysis, t(11;14) was associated with lower rates of subclone formation and hyperdiploidy with higher rates. PC-AL itself lost statistical significance, demonstrating that the lower subclone frequency in AL is a reflection of its exceptionally high t(11;14) frequency. In summary, the subclone patterns in PC-AL and PC-non-AL are closely related, implying that subclone formation depends on the main cytogenetic categories and is independent of disease entity and stage.

| S-EPMC6199662 | biostudies-literature

MicroRNA Expression Profile of serum exosomes from Bortezomib-resistant and Bortezomib-response patients in multiple myeloma

2016-07-31 | GSE71435 | GEO

Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma.

Project description:Although the proteasome inhibitor bortezomib (BTZ) shows excellent efficacy in multiple myeloma (MM), a fraction of patients has a suboptimal or no response to this agent. In addition, BTZ-induced peripheral neuropathy (BiPN), a frequent side-effect of this therapy, limits its use in some patients. This study aimed to explore serum lipid biomarker candidates to predict the response to BTZ and the severity of BiPN. Fifty-nine serum samples were collected from patients with MM prior to receiving BTZ plus low-dose dexamethasone therapy. Serum levels of phospholipids, sphingolipids, neutral lipids, and polyunsaturated fatty acids and their oxidation products were measured by a comprehensive lipidomic study. Overall, 385 lipid metabolites were identified in patients' sera; lower levels of several glycerophospholipids, sphingolipids, and cholesteryl esters were associated with a poor treatment response. Metabolites related to platelet-activating factor biosynthesis and cholesterol metabolism appeared particularly relevant. Furthermore, several lysophosphatidylcholines, phosphatidylcholines, ceramides, neutral lipids, and oxidative fatty acids were significantly increased or decreased in patients with BiPN grades ranging from G0 to G3. Among these compounds, mediators reportedly inducing myelin breakdown and stimulating inflammatory responses were prominent. Although further study is necessary to validate these biomarker candidates, our results contribute to the development of predictive biomarkers for response to BTZ treatment, or ensuing severe BiPN, in patients with MM.

| S-EPMC6778623 | biostudies-literature

Bortezomib combination therapy in multiple myeloma.

Project description:Bortezomib was approved for the treatment of multiple myeloma (MM) in 2003. Since then several bortezomib-based combination therapies have emerged. Although some combinations have been preceded by preclinical investigations, most have followed the inevitable process in which active (or potentially active) drugs are combined with each other to create new treatment regimens. Regimens that have combined bortezomib with corticosteroids, alkylating agents, thalidomide, and/or lenalidomide have resulted in high response rates. Despite the higher and often deeper response rates and prolongation of progression-free survival with bortezomib-based multiagent regimens, an overall survival (OS) advantage has not been demonstrated with most combinations compared to the sequential approach of using anti-myeloma agents, particularly in patients less than 65 years of age with newly diagnosed myeloma. The unique properties of some of these regimens can be taken into account when choosing a particular regimen based on the clinical scenario. For example, the combination of bortezomib, thalidomide, and dexamethasone (VTD) has particular value in renal failure since none of the drugs need dose modification. Similarly, the combination chemotherapy regimen VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) is of particular value in patients presenting with aggressive disease such as extramedullary plasmacytomas or plasma cell leukemia. Ongoing clinical trials are testing combinations of bortezomib with several other classes of agents, including monoclonal antibodies, and inhibitors of deacetylases, heat shock proteins, phosphatidyl inositol 3-kinase/Akt/mammalian target of rapamycin pathway and farnesyl transferase.

| S-EPMC3597231 | biostudies-literature

MicroRNA Expression Profile of serum exosomes from Bortezomib-resistant and Bortezomib-response patients in multiple myeloma

Project description:MicroRNA microarray profilling analysis was performed on exosomes derived from serum in patients with myeloma in two conditions of therapeutic efficacy, Bortezomib resistance and Bortezomib response. Bortezomib is approved and widely used treating myeloma. Two kinds of sample were analyzed. MicroRNA microarray profilling analysis (using miRCURY LNA microRNA Array, 7th generation REV - hsa, mmu & rno, mirBase release 18, ProductNumber=208520,208521,208522) was performed on exosomes derived from serum in patients with myeloma in two conditions of therapeutic efficacy, Bortezomib resistance and Bortezomib response.

2016-07-31 | E-GEOD-71435 | biostudies-arrayexpress

Bortezomib Treatment Modulates Autophagy in Multiple Myeloma.

Project description:Although the introduction of bortezomib as a therapeutic strategy has improved the overall survival of multiple myeloma (MM) patients, 15-20% of high-risk patients do not respond to bortezomib over time or become resistant to treatment. Therefore, the development of new therapeutic strategies, such as combination therapies, is urgently needed. METHODS:Given that bortezomib resistance may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation, and that an enormous amounts of misfolded protein is generated in myeloma plasma cells (PCs), we investigated the effect of the simultaneous inhibition of proteasome by bortezomib and autophagy by hydroxychloroquine (HCQ) treatment on PCs and endothelial cells (ECs) isolated from patients with monoclonal gammopathy of undetermined significance (MGUS) and MM. RESULTS:We found that bortezomib combined with HCQ induces synergistic cytotoxicity in myeloma PCs whereas this effect is lost on ECs. Levels of microtubule-associated protein light chain beta (LC3B) and p62 are differentially modulated in PCs and ECs, with effects on cell viability and proliferation. CONCLUSIONS:Our results suggest that treatment with bortezomib and HCQ should be associated with an anti-angiogenic drug to prevent the pro-angiogenic effect of bortezomib, the proliferation of a small residual tumor PC clone, and thus the relapse.

| S-EPMC7073518 | biostudies-literature

Impact of early response on outcomes in AL amyloidosis following treatment with frontline Bortezomib.

Project description:The outcomes in systemic AL amyloidosis are dependent on the depth of haematologic response. However, there is limited data on the impact of the speed of response on outcomes. Here we report the impact of speed of response in a cohort of AL patients treated with upfront Bortezomib. Patients seen from February 2010 until August 2019 are included in the present analysis. 1194 & 1133 patients comprised the ITT and 1-month landmark cohorts. In the landmark cohort, 137 (11.5%), 270 (22.6%), 252 (21.1%) and 352 (31.1%) patients had a CR, VGPR, PR and NR at 1-month. Patients with ≥ VGPR at 1-month had significantly better survival (median not reached; at the end of 1, 2, 5,10 years, 87%/92%, 83%/87%, 68%/72% and 63%/58% of patients in CR/VGPR, respectively, were alive) compared to those with a PR (median OS 60 months) or NR (median OS 32 months) (p < 0.005). At 1-month, patients with CR and iFLC < 20 mg/l had a significantly better survival compared to CR and iFLC > 20 mg/l (p = 0.005). Reaching ≥ VGPR at 1-month significantly improved survival in all Mayo disease stages. In conclusion, patients achieving an early deep haematologic response have a significantly superior survival irrespective of cardiac involvement.

| S-EPMC8217489 | biostudies-literature

Sequential response-driven bortezomib-based therapy followed by autologous stem cell transplant in AL amyloidosis.

Project description:Autologous stem cell transplant (ASCT) is highly effective in selected patients with light chain (AL) amyloidosis. Bortezomib, preceding or following ASCT, improves responses. Satisfactory responses, including at least a partial response, very good partial response (VGPR) with organ response, or complete response, can be observed after induction therapy alone. We report 139 patients treated upfront with cyclophosphamide/bortezomib/dexamethasone (CyBorD), followed by ASCT only if response was unsatisfactory. Only 1 treatment-related death was observed. After CyBorD, hematologic response (HR) rate was 68% (VGPR or better, 51%), with 45% satisfactory responses. Transplant was performed in 55 (40%) subjects and resulted in an 80% HR rate (65% ≥ VGPR). Five-year survival was 86% and 84% in patients treated with ASCT or CyBorD alone, respectively (P = .438). Also, 6- and 12- month landmark analyses did not show differences in survival. Duration of response was not different in the 2 groups (60 vs 49 months; P = .670). Twenty-one (15%) patients with an unsatisfactory response to CyBorD could not undergo ASCT because of ineligibility or refusal; instead, they received rescue chemotherapy, with HR in 38% of cases and 51% 5-year survival. This sequential response-driven approach, offering ASCT to patients who do not attain satisfactory response to upfront CyBorD, is very safe and effective in AL amyloidosis.

| S-EPMC7479942 | biostudies-literature

Outcomes of bortezomib combination chemotherapies in autologous stem cell transplantation-ineligible patients with AL amyloidosis.

Project description:BackgroundTreatment protocols for light chain (AL) amyloidosis have been derived from myeloma treatment. Bortezomib is a key drug used for the treatment of myeloma and AL amyloidosis. We retrospectively investigated the efficacy and toxicity of bortezomib- based chemotherapy in patients with newly diagnosed AL amyloidosis.MethodsWe reviewed the outcomes of newly diagnosed autologous stem cell transplantation (auto-SCT)-ineligible AL amyloidosis patients who received bortezomib-based chemotherapy at a referral center between 2011 and 2017.ResultsOf 63 patients who received bortezomib-based chemotherapy, 32 were male, and the median age was 66 years (range, 42‒82 yr). The hematologic overall response rate (ORR) was 65.1%, and the chemotherapy regimen with the best hematologic response was VMP (75.7%, 28/37). Sixty patients had significant organ (heart or kidney) involvement; 28.3% of patients (N=17) had major organ responses after chemotherapy. With a median follow- up of 34 months, there was no significant difference in progression-free survival (P=0.49) or overall survival (P =0.67) according to regimen. Most hematologic and non-hematologic problems were manageable.ConclusionVarious chemotherapy combinations based on bortezomib are currently employed in the clinical setting, but no difference was found in terms of efficacy or toxicity.

| S-EPMC8721454 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data