TY  - JOUR
A1  - Lückerath, Katharina
A1  - Lapa, Constantin
A1  - Albert, Christa
A1  - Herrmann, Ken
A1  - Jörg, Gerhard
A1  - Samnick, Samuel
A1  - Einsele, Herrmann
A1  - Knop, Stefan
A1  - Buck, Andreas K.
T1  - \(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma
JF  - Oncotarget
N2  - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
KW  - positron emission tomography
KW  - imaging techniques
KW  - experience
KW  - \(^{11}\)C-Methionine-PET
KW  - treatment response
KW  - molecular imaging
KW  - multiple myeloma
KW  - management
KW  - \(^{18}\)F-FDG PET/CT
KW  - bone disease
KW  - stem-cell transplantation
KW  - esophagogastric junction
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148688
VL  - 6
IS  - 10
ER  - 
TY  - JOUR
A1  - Dimopoulos, Meletios A.
A1  - Weisel, Katja C.
A1  - Song, Kevin W.
A1  - Delforge, Michel
A1  - Karlin, Lionel
A1  - Goldschmidt, Hartmut
A1  - Moreau, Philippe
A1  - Banos, Anne
A1  - Oriol, Albert
A1  - Garderet, Laurent
A1  - Cavo, Michele
A1  - Ivanova, Valentina
A1  - Alegre, Adrian
A1  - Martinez-Lopez, Joaquin
A1  - Chen, Christine
A1  - Spencer, Andrew
A1  - Knop, Stefan
A1  - Bahlis, Nizar J.
A1  - Renner, Christoph
A1  - Yu, Xin
A1  - Hong, Kevin
A1  - Sternas, Lars
A1  - Jacques, Christian
A1  - Zaki, Mohamed H.
A1  - San Miguel, Jesus F.
T1  - Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone
JF  - Haematologica
N2  - Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P < 0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or highdose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4; 14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14).
KW  - translocation
KW  - plus dexamethasone
KW  - deletion 17P
KW  - bortezomib
KW  - therapy
KW  - abnormalities
KW  - stem-cell transplantation
KW  - growth-factor receptor 3
KW  - high-risk cytogenetics
KW  - intergroupe francophone
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140349
VL  - 100
IS  - 10
SP  - 1327
EP  - 1333
ER  -