@article{ZhouFluechterNickeletal.2020, author = {Zhou, Xiang and Fl{\"u}chter, Patricia and Nickel, Katharina and Meckel, Katharina and Messerschmidt, Janin and B{\"o}ckle, David and Knorz, Sebastian and Steinhardt, Maximilian Johannes and Krummenast, Franziska and Danhof, Sophia and Einsele, Hermann and Kort{\"u}m, K. Martin and Rasche, Leo}, title = {Carfilzomib based treatment strategies in the management of relapsed/refractory multiple myeloma with extramedullary disease}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers12041035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203704}, year = {2020}, abstract = {Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40-80) years. Twenty (44\%) and 25 (56\%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59\%. Extramedullary response was evaluable in 33 patients, nine (27\%) of them achieved partial remission (PR) (ORR = 27\%). In 15 (33\%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95\% CI, 3.5-6.5) and ten (95\% CI, 7.5-12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.}, language = {en} } @article{ZhouDierksKertelsetal.2020, author = {Zhou, Xiang and Dierks, Alexander and Kertels, Olivia and Samnick, Samuel and Kircher, Malte and Buck, Andreas K. and Haertle, Larissa and Knorz, Sebastian and B{\"o}ckle, David and Scheller, Lukas and Messerschmidt, Janin and Barakat, Mohammad and Truger, Marietta and Haferlach, Claudia and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, K. Martin and Lapa, Constantin}, title = {The link between cytogenetics/genomics and imaging patterns of relapse and progression in patients with relapsed/refractory multiple myeloma: a pilot study utilizing 18F-FDG PET/CT}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {9}, issn = {2072-6694}, doi = {10.3390/cancers12092399}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211157}, year = {2020}, abstract = {Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1-10) lines of therapy. Six (25\%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.}, language = {en} } @article{ZhouDierksKertelsetal.2020, author = {Zhou, Xiang and Dierks, Alexander and Kertels, Olivia and Kircher, Malte and Schirbel, Andreas and Samnick, Samuel and Buck, Andreas K. and Knorz, Sebastian and B{\"o}ckle, David and Scheller, Lukas and Messerschmidt, Janin and Barakat, Mohammad and Kort{\"u}m, K. Martin and Rasche, Leo and Einsele, Hermann and Lapa, Constantin}, title = {18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {8}, issn = {2072-6694}, doi = {10.3390/cancers12082333}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211240}, year = {2020}, abstract = {This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.}, language = {en} } @article{SteinhardtZhouKrummenastetal.2020, author = {Steinhardt, Maximilian Johannes and Zhou, Xiang and Krummenast, Franziska and Meckel, Katharina and Nickel, Katharina and B{\"o}ckle, David and Messerschmidt, Janin and Knorz, Sebastian and Dierks, Alexander and Heidemeier, Anke and Lapa, Constantin and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Klaus Martin}, title = {Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma}, series = {International Journal of Immunopathology and Pharmacology}, volume = {34}, journal = {International Journal of Immunopathology and Pharmacology}, doi = {10.1177/2058738420980258}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236235}, pages = {1-5}, year = {2020}, abstract = {We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab ("Pom-PAD-Dara"), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.}, language = {en} }