A5009510613- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- Calcium signaling and nucleotide metabolism
- Quinazolinone synthesis and applications
- Synthesis and Biological Evaluation
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- HIV/AIDS drug development and treatment
- PI3K/AKT/mTOR signaling in cancer
- Cancer Treatment and Pharmacology
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Helminth infection and control
- Blood disorders and treatments
University of Southern Denmark
2014-2024
Odense University Hospital
2021-2024
Vejle Sygehus
2013-2019
Region of Southern Denmark
2019
Amsterdam UMC Location Vrije Universiteit Amsterdam
2016-2018
Vrije Universiteit Amsterdam
2018
Amsterdam University Medical Centers
2018
Lillebaelt Hospital
2014
Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in phase 1-2 trial involving patients with relapsed or that was refractory to two more prior lines of therapy.In part 1, the dose-escalation phase, we administered daratumumab at doses 0.005 24 mg per kilogram body weight. In 2, dose-expansion 30 received 8 and 42 16 kilogram, once weekly (8 doses), twice monthly for up months. End points included safety, efficacy,...
Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma cells. The aim this study was to investigate the clinical implications and underlying mechanisms daratumumab-mediated reduction.
Abstract Daratumumab is a CD38‐targeted human monoclonal antibody with direct anti‐myeloma cell mechanisms of action. Flow cytometry in relapsed and/or refractory multiple myeloma (RRMM) patients treated daratumumab revealed cytotoxic T‐cell expansion and reduction immune‐suppressive populations, suggesting immune modulation as an additional mechanism Here, we performed in‐depth analysis the effects on immune‐cell subpopulations using high‐dimensional mass cytometry. Whole‐blood bone‐marrow...
8512^ Background: Daratumumab (DARA) is a human CD38 monoclonal antibody (mAb) with broad-spectrum killing activity. Preliminary safety and efficacy data from this first-in-human dose-escalation study of DARA in pts relapsed or refractory (RR) multiple myeloma (MM) have previously been published. Here, we present the finalized part 1 preliminary ongoing 2 study. Methods: Pts ≥18 years requiring systemic therapy considered RR to at least prior lines ineligible for ASCT were enrolled. In 1,...
8533 Background: Daratumumab (DARA) (HuMax-CD38), a human IgG1κ monoclonal antibody effectively mediates destruction of CD38-expressing malignant plasma cells. In the first-in-human dose-escalation study, 42% heavily pretreated patients with relapsed or relapsed, refractory (RR) multiple myeloma (MM) treated DARA alone (≥4mg/kg) achieved partial response (PR) and 25% had minimal (MR) (modified IMWG guidelines). preclinical studies, + lenalidomide (LEN) enhanced killing MM cells in vitro.We...
8513 Background: Pts with RR MM received DARA for 9 wks in doses of 0.005-24mg/kg the GEN501 dose-escalation part (Lokhorst: EHA 2013 abstract S576). The purpose expansion part, which has completed enrollment, was to evaluate safety and efficacy 2 up 24 mths using alternate dose schedules. Methods: ≥18 yrs, at least prior lines therapy, incl. IMiDs proteasome inhibitors, ineligible ASCT were enrolled levels: A: 8mg/kg +/- pre-dose (10mg) wkly first 8 infusions.B: 16mg/kg without a 3-wk...
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells due to constitutive B-cell receptor (BCR) signaling, leading apoptosis resistance and increased proliferation. This study evaluates effects Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib on molecular composition, clonality, kinetics during treatment in CLL patients. Employing a multi-omics approach up 3.2 years follow-up, we analyzed data from 24 patients, specifically focusing nine patients treated with...
<p>Monocytes take up AF488-labeled daratumumab-CD38 complexes from PKH-26-stained UM9 cells.</p>
<p>Daratumumab is transferred from UM9 cells to monocytes.</p>
<p>Daratumumab-mediated CD38 reduction of MM cells in the presence PBMCs as shown by Western blot analysis.</p>
<p>Supplemental Methods, Supplementary Tables, Figure Legends</p>
<p>Supplemental Methods, Supplementary Tables, Figure Legends</p>