@article{PhilippAbbrederisHerrmannKnopetal.2015, author = {Philipp-Abbrederis, Kathrin and Herrmann, Ken and Knop, Stefan and Schottelius, Margret and Eiber, Matthias and L{\"u}ckerath, Katharina and Pietschmann, Elke and Habringer, Stefan and Gerngroß, Carlos and Franke, Katharina and Rudelius, Martina and Schirbel, Andreas and Lapa, Constantin and Schwamborn, Kristina and Steidle, Sabine and Hartmann, Elena and Rosenwald, Andreas and Kropf, Saskia and Beer, Ambros J and Peschel, Christian and Einsele, Hermann and Buck, Andreas K and Schwaiger, Markus and G{\"o}tze, Katharina and Wester, Hans-J{\"u}rgen and Keller, Ulrich}, title = {In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma}, series = {EMBO Molecular Medicine}, volume = {7}, journal = {EMBO Molecular Medicine}, number = {4}, doi = {10.15252/emmm.201404698}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148738}, pages = {477-487}, year = {2015}, abstract = {CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.}, language = {en} } @article{HausmannBrandtKoecheletal.2015, author = {Hausmann, Stefan and Brandt, Evelyn and K{\"o}chel, Carolin and Einsele, Hermann and Bargou, Ralf C. and Seggewiss-Bernhardt, Ruth and St{\"u}hmer, Thorsten}, title = {Loss of serum and glucocorticoid-regulated kinase 3 (SGK3) does not affect proliferation and survival of multiple myeloma cell lines}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0122689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148708}, pages = {e0122689}, year = {2015}, abstract = {Multiple myeloma (MM) is a generally fatal plasma cell cancer that often shows activation of the phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway. Targeted pharmacologic therapies, however, have not yet progressed beyond the clinical trial stage, and given the complexity of the PI3K/Akt signalling system (e.g. multiple protein isoforms, diverse feedback regulation mechanisms, strong variability between patients) it is mandatory to characterise its ramifications in order to better guide informed decisions about the best therapeutic approaches. Here we explore whether serum and glucocorticoid-regulated kinase 3 (SGK3), a potential downstream effector of PI3K, plays a role in oncogenic signalling in MM cells-either in concert with or independent of Akt. SGK3 was expressed in all MM cell lines and in all primary MM samples tested. Four MM cell lines representing a broad range of intrinsic Akt activation (very strong: MM. 1s, moderate: L 363 and JJN-3, absent: AMO-1) were chosen to test the effects of transient SGK3 knockdown alone and in combination with pharmacological inhibition of Akt, PI3K-p110\(\alpha\), or in the context of serum starvation. Although the electroporation protocol led to strong SGK3 depletion for at least 5 days its absence had no substantial effect on the activation status of potential downstream substrates, or on the survival, viability or proliferation of MM cells in all experimental contexts tested. We conclude that it is unlikely that SGK3 plays a significant role for oncogenic signalling in multiple myeloma.}, language = {en} } @article{AndersenBogstedDybkaretal.2015, author = {Andersen, Jens Peter and B{\o}gsted, Martin and Dybk{\ae}r, Karen and Mellqvist, Ulf-Henrik and Morgan, Gareth J. and Goldschmidt, Hartmut and Dimopoulos, Meletios A. and Einsele, Hermann and San Miguel, Jes{\´u}s and Palumbo, Antonio and Sonneveld, Pieter and Johnsen, Hans Erik}, title = {Global myeloma research clusters, output, and citations: a bibliometric mapping and clustering analysis}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0116966}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144214}, pages = {e0116966}, year = {2015}, abstract = {Background International collaborative research is a mechanism for improving the development of disease-specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases. Methods and Findings We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and co-authorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43\% increase. This increase is high compared to the 24\% and 14\% increases observed for lymphoma and leukaemia. The major proportion (> 90\% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. Conclusion and Perspective Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care.}, language = {en} } @article{TerposKleberEngelhardtetal.2015, author = {Terpos, Evangelos and Kleber, Martina and Engelhardt, Monika and Zweegman, Sonja and Gay, Francesca and Kastritis, Efstathios and van de Donk, Niels W. C. J. and Bruno, Benedetto and Sezer, Orhan and Broijl, Annemiek and Bringhen, Sara and Beksac, Meral and Larocca, Alessandra and Hajek, Roman and Musto, Pellegrino and Johnsen, Hans Erik and Morabito, Fortunato and Ludwig, Heinz and Cavo, Michele and Einsele, Hermann and Sonneveld, Pieter and Dimopoulos, Meletios A. and Palumbo, Antonio}, title = {European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications}, series = {Haematologica}, volume = {100}, journal = {Haematologica}, number = {10}, doi = {10.3324/haematol.2014.117176}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141913}, pages = {1254 -- 1266}, year = {2015}, abstract = {The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging. In asymptomatic myeloma, bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given continuously, but it is not clear if patients who achieve at least a very good partial response benefit from its continuous use (grade 1B). Treatment with erythropoietic-stimulating agents may be initiated in patients with persistent symptomatic anemia (hemoglobin < 10g/dL) in whom other causes of anemia have been excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if no adequate hemoglobin response is achieved. For renal impairment, bortezomib-based regimens are the current standard of care (grade 1A). For the management of treatment-induced peripheral neuropathy, drug modification is needed (grade 1C). Vaccination against influenza is recommended; vaccination against streptococcus pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or valacyclovir) is recommended for patients receiving proteasome inhibitors, autologous or allogeneic transplantation (grade 1A).}, language = {en} } @article{DanhofSchrederStrifleretal.2015, author = {Danhof, Sophia and Schreder, Martin and Strifler, Susanne and Einsele, Hermann and Knop, Stefan}, title = {Long-Term Disease Control by Pomalidomide-/Dexamethasone-Based Therapy in a Patient with Advanced Multiple Myeloma: A Case Report and Review of the Literature}, series = {Case Reports in Oncology}, volume = {8}, journal = {Case Reports in Oncology}, number = {1}, doi = {10.1159/000381983}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126093}, pages = {189-195}, year = {2015}, abstract = {Background: Therapy for multiple myeloma (MM) has substantially improved in the era of immunomodulatory drugs and bortezomib. However, the prognosis of patients with progressive disease despite treatment with these 'novel agents' remains poor. Recently, pomalidomide was approved in this setting, but a median progression-free survival of <4 months still leaves room for improvement. Pomalidomide-based combination therapies are currently under investigation, but data on long-term treatment are lacking. Case Report: We present the case of a 68-year-old woman with refractory MM who received pomalidomide in combination with various drugs including anthracyclines, alkylators and proteasome inhibitors. Initially, major hematological toxicities and infectious complications including a hepatitis B virus reactivation were encountered. With careful dose adjustments and selection of combination partners, pomalidomide treatment was maintained for over 4 years and led to a sustained partial remission. In particular, the well-tolerated regimen of bortezomib, cyclophosphamide and dexamethasone together with pomalidomide was administered for >30 cycles. Conclusion: This case illustrates the value of an individualized approach to myeloma care given an increasing availability of 'novel agents'. Tailored treatment using these drugs as a backbone is essential to achieve long-lasting responses and minimize side effects.}, language = {en} }