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Open Access 01-06-2021 | Elotuzumab | Original Article

Elotuzumab for the treatment of extramedullary myeloma: a retrospective analysis of clinical efficacy and SLAMF7 expression patterns

Authors: Sophia Danhof, Leo Rasche, Anja Mottok, Tabea Steinmüller, Xiang Zhou, Martin Schreder, Teresa Kilian, Susanne Strifler, Andreas Rosenwald, Michael Hudecek, Hermann Einsele, Elena Gerhard-Hartmann

Published in: Annals of Hematology | Issue 6/2021

Abstract

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.

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Title: Elotuzumab for the treatment of extramedullary myeloma: a retrospective analysis of clinical efficacy and SLAMF7 expression patterns
Authors: Sophia Danhof
Leo Rasche
Anja Mottok
Tabea Steinmüller
Xiang Zhou
Martin Schreder
Teresa Kilian
Susanne Strifler
Andreas Rosenwald
Michael Hudecek
Hermann Einsele
Elena Gerhard-Hartmann
Publication date: 01-06-2021
Publisher: Springer Berlin Heidelberg
Keyword: Elotuzumab
Published in: Annals of Hematology / Issue 6/2021
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-021-04447-6

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