TY  - JOUR
A1  - Rasche, Leo
A1  - Kumar, Manoj
A1  - Gershner, Grant
A1  - Samant, Rohan
A1  - Van Hemert, Rudy
A1  - Heidemeier, Anke
A1  - Lapa, Constantin
A1  - Bley, Thorsten
A1  - Buck, Andreas
A1  - McDonald, James
A1  - Hillengass, Jens
A1  - Epstein, Joshua
A1  - Thanendrarajan, Sharmilan
A1  - Schinke, Carolina
A1  - van Rhee, Frits
A1  - Zangari, Maurizio
A1  - Barlogie, Bart
A1  - Davies, Faith E.
A1  - Morgan, Gareth J.
A1  - Weinhold, Niels
T1  - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis?
JF  - Theranostics
N2  - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM.
KW  - multiple myeloma
KW  - diffusion weighted mri
KW  - spleen
KW  - tumor burden
KW  - high risk
KW  - extramedullary hematopoiesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982
VL  - 9
IS  - 16
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Dierks, Alexander
A1  - Kertels, Olivia
A1  - Samnick, Samuel
A1  - Kircher, Malte
A1  - Buck, Andreas K.
A1  - Haertle, Larissa
A1  - Knorz, Sebastian
A1  - Böckle, David
A1  - Scheller, Lukas
A1  - Messerschmidt, Janin
A1  - Barakat, Mohammad
A1  - Truger, Marietta
A1  - Haferlach, Claudia
A1  - Einsele, Hermann
A1  - Rasche, Leo
A1  - Kortüm, K. Martin
A1  - Lapa, Constantin
T1  - 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
JF  - Cancers
N2  - 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.
KW  - radiogenomics
KW  - 18F-FDG PET/CT
KW  - multiple myeloma
KW  - relapse
KW  - progression
KW  - pattern
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211157
SN  - 2072-6694
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Steinhardt, Maximilian Johannes
A1  - Zhou, Xiang
A1  - Krummenast, Franziska
A1  - Meckel, Katharina
A1  - Nickel, Katharina
A1  - Böckle, David
A1  - Messerschmidt, Janin
A1  - Knorz, Sebastian
A1  - Dierks, Alexander
A1  - Heidemeier, Anke
A1  - Lapa, Constantin
A1  - Einsele, Hermann
A1  - Rasche, Leo
A1  - Kortüm, Klaus Martin
T1  - Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma
JF  - International Journal of Immunopathology and Pharmacology
N2  - 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.
KW  - CD38
KW  - MOR202
KW  - daratumumab
KW  - multiple myeloma
KW  - refractory
KW  - relapse
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236235
VL  - 34
ER  - 
TY  - JOUR
A1  - Grunz, Jan-Peter
A1  - Kunz, Andreas Steven
A1  - Baumann, Freerk T.
A1  - Hasenclever, Dirk
A1  - Sieren, Malte Maria
A1  - Heldmann, Stefan
A1  - Bley, Thorsten Alexander
A1  - Einsele, Hermann
A1  - Knop, Stefan
A1  - Jundt, Franziska
T1  - Assessing osteolytic lesion size on sequential CT scans is a reliable study endpoint for bone remineralization in newly diagnosed multiple myeloma
JF  - Cancers
N2  - Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis.
KW  - multiple myeloma
KW  - bone remineralization
KW  - computed tomography
KW  - whole-body imaging
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-362526
SN  - 2072-6694
VL  - 15
IS  - 15
ER  -