A5011515629- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Hematological disorders and diagnostics
- Sarcoma Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Chemokine receptors and signaling
- Bone health and treatments
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Chronic Myeloid Leukemia Treatments
- Synthesis and Biological Evaluation
- Immunotherapy and Immune Responses
- Malaria Research and Control
- Lymphoma Diagnosis and Treatment
University of Arkansas for Medical Sciences
2016-2025
Winthrop Rockefeller Foundation
2020-2024
John Wiley & Sons (United States)
2021
Hudson Institute
2021
Netherlands Comprehensive Cancer Organisation
2019
University of Arkansas Medical Center
2019
Myeloma UK
2017-2018
Cancer Research And Biostatistics
2015
International Myeloma Foundation
2015
University of Bonn
2011-2012
Abstract In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of “fitter” clones may be anticipated. However, an imbalanced distribution frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into spatial clonal architecture. We demonstrate genomic heterogeneity more than 75% patients,...
Abstract The use of bispecific antibodies (BsAbs) in the treatment relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates heavily pretreated patients. Infectious complications related to BsAbs are not well described. We conducted a pooled analysis that included all single-agent used MM with no prior different BsAbs. A total 1185 patients were treated BsAb studied period (71.6% an agent targeting B-cell maturation antigen (BCMA). Pooled median follow-up...
Abstract The objective of our study was to report real-world data on the safety and efficacy standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort included all consecutive that received at least one dose up until August 2023. One hundred ten were included, whom, 86% had triple-class refractory disease, 76% penta-refractory 35% prior exposure B-cell maturation antigen (BCMA)-targeting therapies. overall...
Abstract Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T of are rare. One potential reason is that small subset minimal residual cells seeds relapse. Residual BCMA-CAR-T-mediated show less-differentiated features and express stem-like genes, including CD24. CD24-positive large fraction after BCMA-CAR-T therapy....
Abstract Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions semiquantitative characterization metabolic activity (glycolytic phenotype) by calculation glucose uptake. Total lesion glycolysis (TLG) tumor volume (MTV) have potential to improve value this approach enhance prognostic disease burden measures. This study aims determine whether TLG MTV are associated...
Smoldering myeloma (SMM) is associated with a high-risk of progression to (MM). We report the results study 82 patients both targeted sequencing that included capture immunoglobulin and MYC regions. By comparing these newly diagnosed (MM) we show fewer NRAS FAM46C mutations together adverse translocations, del(1p), del(14q), del(16q), del(17p) in SMM consistent their role as drivers transition MM. KRAS are shorter time (HR 3.5 (1.5-8.1), p = 0.001). In an analysis change clonal structure...
Abstract As multiple myeloma (MM) treatments evolve, frequent updates are required to monitor the long-term effect of changes in approach. Traditionally, MM is considered an incurable disease, with most patients eventually relapsing. However, improvements has raised possibility that might be functionally curable. To examine survival, we followed 4329 newly diagnosed treated autologous stem cell transplantation (ASCT) at University Arkansas for Medical Sciences from 1989 through 2018. Overall...
Deciphering Multiple Myeloma evolution in the whole bone marrow is key to inform curative strategies. Here, we perform spatial-longitudinal whole-exome sequencing, including 140 samples collected from 24 patients during up 14 years. Applying imaging-guided sampling observe three evolutionary patterns, relapse driven by a single-cell expansion, competing/co-existing sub-clones, and unique sub-clones at distinct locations. While do not find sub-clone baseline focal lesion(s), show close...
The use of chimeric antigen receptor-T cell (CAR-T) therapy and bispecific antibodies in multiple myeloma is expanding, with encouraging early results. It unknown if the current geographic distribution CAR-T allows access for patients need, especially Black populations, which have a higher incidence myeloma.To investigate equitable myeloma.This cross-sectional study data from clinical trials all available studies listed ClinicalTrials.gov until January 31, 2022. Only 1 or more open sites US...
Disparities that affect Black persons with various hematological malignant neoplasms are substantial, yet little is known about disparities related to the use of US Food and Drug Administration (FDA)-approved chimeric antigen receptor-T cell (CAR-T) therapy.To examine enrollment participants in clinical trials resulted a subsequent FDA approval CAR-T products neoplasms.A cross-sectional study was performed using publicly available data on drug demographic subgroups from Drugs@fda period...
There is a paucity of granular data on infection risk with B-cell maturation antigen (BMCA) and GPRC5D bispecific antibodies (bsAb) in relapsed/refractory multiple myeloma (RRMM). The aim our multi-institutional study was to characterize the incidence, etiologies, factors infections from start therapy last follow-up or 90 days after exit. A total 66 patients received BCMA bsAb monotherapy, 15 combination daratumumab and/or pomalidomide. While rate per 100 0.57 for bsAb, it 0.62 0.13...
Abstract Early alterations within the bone marrow microenvironment that contribute to progression of multiple myeloma (MM) from its precursor stages could be key identifying novel therapeutic approaches. However, intrinsic variability in cellular populations between patients and differences sample processing analysis methods have made it difficult identify consistent changes data sets. Here, we used single-cell RNA sequencing cells stages, monoclonal gammopathy unknown significance,...
Fluorine-18 fluorodeoxyglucose positron emission tomography with computed attenuation correction (PET-CT) in myeloma can detect and enumerate focal lesions by the quantitative characterization of metabolic activity. The aim this study was to determine prognostic significance suppression PET-CT activity at a number time points post therapy initiation: day 7, induction, transplant, maintenance therapy. As part TT4-6 trial series, 596 patients underwent baseline were evaluated serially during...
Abstract The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted 578 individuals with plasma cell neoplasms the FoundationOne Heme identified relevant abnormalities novel markers. Mutational burden was associated maf proliferation gene expression groups, high-mutational poor prognosis. homozygous deletions that were present myeloma within key genes, including CDKN2C , RB1,...
Copy-number changes and translocations have been studied extensively in many datasets with long-term follow-up. The impact of mutations remains debated given the short time to follow-up most datasets.We performed targeted panel sequencing covering 125 myeloma-specific genes loci involved 223 newly diagnosed myeloma samples recruited into one total therapy trials.As expected, commonly mutated were NRAS, KRAS, BRAF, making up 44% patients. Double-Hit BRAF DIS3 had an on outcome alongside...
Multiple myeloma (MM) growth is supported by an immune-tolerant bone marrow microenvironment. Here, we find that loss of Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) tumor microenvironmental cells associated with MM suppression. The absence NEK2 leads to both fewer tumor-associated macrophages (TAMs) and inhibitory T cells. expression myeloid progenitor promotes the generation functional TAMs when stimulated conditional medium. Clinically, high increased CD8+ effector memory cells,...
Light chain deposition disease (LCDD) is characterized by monotypic immunoglobulin depositions which will eventually lead to loss of organ function if left untreated. While the kidney almost always affected, presence and degree LCDD in other organs vary. Ten thirty percent patients have underlying Multiple Myeloma (MM), yet outcome prognostic markers this particular patient group are still lacking. Here, we analyzed 69 with MM biopsy proven report on renal extra-renal involvement its impact...