Abstract
Based on ELOQUENT-2, combination therapy with the monoclonal antibody elotuzumab was approved for relapsed/refractory multiple myeloma in the US and Europe. However, outside clinical trials, the optimal integration of elotuzumab into the sequence of treatment lines remains to be determined. Therefore, we analyzed safety and efficacy of elotuzumab/immunomodulatory drug combinations in a real-life cohort of 33 patients from our institution. The most frequent grade 3/4 adverse event was lymphopenia which did not increase the incidence of viral reactivations. After a median of four prior treatment lines, an overall response rate of 60% and a median progression-free survival (PFS) of 8 months were observed. The presence of cytogenetic high-risk status had no impact on PFS while low disease burden and high numbers of natural killer (NK)-cells at treatment initiation were associated with longer PFS. We observed an extramedullary relapse in three patients, associated with reduced expression of the elotuzumab target antigen SLAMF7 on extramedullary myeloma cells in one patient. Thus, biomarkers like disease burden, NK-cell count and SLAMF7 expression on myeloma cells may help to define myeloma patients with high likelihood to respond to elotuzumab treatment. Prospective trials investigating these biomarkers in larger patient cohorts are highly warranted.
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SD was supported by the Else Kröner-Forschungskolleg Würzburg, Germany.
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SD, SK and MS designed the research study; SD, SS, DH and MS performed the research; SS, MB, HE and MS contributed essential research material; SD, MK, MB and JH analyzed the data; HE supervised the project; SD drafted the manuscript; SS, DH, MK, MB, JH, HE, SK and MS carefully revised the manuscript; all authors approved the final version of the manuscript.
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SK: honoraria from Celgene GmbH and Bristol-Myers Squibb GmbH. SD, MS: Advisory Board for Bristol-Myers Squibb GmbH.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants for whom biospecimens were included in the study.
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Danhof, S., Strifler, S., Hose, D. et al. Clinical and biological characteristics of myeloma patients influence response to elotuzumab combination therapy. J Cancer Res Clin Oncol 145, 561–571 (2019). https://doi.org/10.1007/s00432-018-2807-1
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DOI: https://doi.org/10.1007/s00432-018-2807-1