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  - Rasche, Leo
A1  - Kortüm, K. Martin
A1  - Raab, Marc S.
A1  - Weinhold, Niels
T1  - The impact of tumor heterogeneity on diagnostics and novel therapeutic strategies in multiple myeloma
JF  - International Journal of Molecular Sciences
N2  - Myeloma is characterized by extensive inter-patient genomic heterogeneity due to multiple different initiating events. A recent multi-region sequencing study demonstrated spatial differences, with progression events, such as TP53 mutations, frequently being restricted to focal lesions. In this review article, we describe the clinical impact of these two types of tumor heterogeneity. Target mutations are often dominant at one site but absent at other sites, which poses a significant challenge to personalized therapy in myeloma. The same holds true for high-risk subclones, which can be locally restricted, and as such not detectable at the iliac crest, which is the usual sampling site. Imaging can improve current risk classifiers and monitoring of residual disease, but does not allow for deciphering the molecular characteristics of tumor clones. In the era of novel immunotherapies, the clinical impact of heterogeneity certainly needs to be re-defined. Yet, preliminary observations indicate an ongoing impact of spatial heterogeneity on the efficacy of monoclonal antibodies. In conclusion, we recommend combining molecular tests with imaging to improve risk prediction and monitoring of residual disease. Overcoming intra-tumor heterogeneity is the prerequisite for curing myeloma. Novel immunotherapies are promising but research addressing their impact on the spatial clonal architecture is highly warranted.
KW  - multiple myeloma
KW  - spatial heterogeneity
KW  - risk stratification
KW  - minimal residual disease
KW  - targeted therapy
KW  - clinical imaging
KW  - immunotherapy
KW  - daratumumab
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285402
SN  - 1422-0067
VL  - 20
IS  - 5
ER  -