TY  - JOUR
A1  - Danhof, Sophia
A1  - Rasche, Leo
A1  - Mottok, Anja
A1  - Steinmüller, Tabea
A1  - Zhou, Xiang
A1  - Schreder, Martin
A1  - Kilian, Teresa
A1  - Strifler, Susanne
A1  - Rosenwald, Andreas
A1  - Hudecek, Michael
A1  - Einsele, Hermann
A1  - Gerhard-Hartmann, Elena
T1  - Elotuzumab for the treatment of extramedullary myeloma: a retrospective analysis of clinical efficacy and SLAMF7 expression patterns
JF  - Annals of Hematology
N2  - Extramedullary disease (EMD) represents a high-risk state of multiple myeloma (MM) associated with poor prognosis. While most anti-myeloma therapeutics demonstrate limited efficacy in this setting, some studies exploring the utility of chimeric antigen receptor (CAR)-modified T cells reported promising results. We have recently designed SLAMF7-directed CAR T cells for the treatment of MM. SLAMF7 is a transmembrane receptor expressed on myeloma cells that plays a role in myeloma cell homing to the bone marrow. Currently, the only approved anti-SLAMF7 therapeutic is the monoclonal antibody elotuzumab, but its efficacy in EMD has not been investigated thoroughly. Thus, we retrospectively analyzed the efficacy of elotuzumab-based combination therapy in a cohort of 15 patients with EMD. Moreover, since the presence of the target antigen is an indispensable prerequisite for effective targeted therapy, we investigated the SLAMF7 expression on extramedullary located tumor cells before and after treatment. We observed limited efficacy of elotuzumab-based combination therapies, with an overall response rate of 40% and a progression-free and overall survival of 3.8 and 12.9 months, respectively. Before treatment initiation, all available EMD tissue specimens (n = 3) demonstrated a strong and consistent SLAMF7 surface expression by immunohistochemistry. Furthermore, to investigate a potential antigen reduction under therapeutic selection pressure, we analyzed samples of de novo EMD (n = 3) outgrown during elotuzumab treatment. Again, immunohistochemistry documented strong and consistent SLAMF7 expression in all samples. In aggregate, our data point towards a retained expression of SLAMF7 in EMD and encourage the development of more potent SLAMF7-directed immunotherapies, such as CAR T cells.
KW  - plasma cells
KW  - extramedullary disease
KW  - monoclonal antibody
KW  - CD319
KW  - CS1
KW  - antigen loss
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266468
SN  - 1432-0584
VL  - 100
IS  - 6
ER  - 
TY  - JOUR
A1  - Zhou, Xiang
A1  - Flüchter, Patricia
A1  - Nickel, Katharina
A1  - Meckel, Katharina
A1  - Messerschmidt, Janin
A1  - Böckle, David
A1  - Knorz, Sebastian
A1  - Steinhardt, Maximilian Johannes
A1  - Krummenast, Franziska
A1  - Danhof, Sophia
A1  - Einsele, Hermann
A1  - Kortüm, K. Martin
A1  - Rasche, Leo
T1  - Carfilzomib based treatment strategies in the management of relapsed/refractory multiple myeloma with extramedullary disease
JF  - Cancers
N2  - 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.
KW  - carfilzomib
KW  - extramedullary disease
KW  - multiple myeloma
KW  - relapse
KW  - refractory
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203704
SN  - 2072-6694
VL  - 12
IS  - 4
ER  -