Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing
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- dc.contributor.author Majumder, Muntasir Mamun
- dc.contributor.author Silvennoinen, Raija
- dc.contributor.author Anttila, Pekka
- dc.contributor.author Tamborero Noguera, David
- dc.contributor.author Eldfors, Samuli
- dc.contributor.author Yadav, Bhagwan
- dc.contributor.author Karjalainen, Riikka
- dc.contributor.author Kuusanmäki, Heikki
- dc.contributor.author Lievonen, Juha
- dc.contributor.author Parsons, Alun
- dc.contributor.author Suvela, Minna
- dc.contributor.author Jantunen, Esa
- dc.contributor.author Porkka, Kimmo
- dc.contributor.author Heckman, Caroline A.
- dc.date.accessioned 2024-01-16T06:55:02Z
- dc.date.available 2024-01-16T06:55:02Z
- dc.date.issued 2017
- dc.description.abstract Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.
- dc.description.sponsorship The study was funded by a research grant from Celgene. DT is supported by a Marie Curie Actions of the Seventh Framework Programme of the European Union (FP7/2007-2013) under REA grant agreement number 600388 and by the Agency of Competitiveness for Companies of the Government of Catalonia, ACCIO.
- dc.format.mimetype application/pdf
- dc.identifier.citation Majumder MM, Silvennoinen R, Anttila P, Tamborero D, Eldfors S, Yadav B, et al. Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing. Oncotarget. 2017 Aug 22;8(34):56338-50. DOI: 10.18632/oncotarget.17630
- dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.17630
- dc.identifier.issn 1949-2553
- dc.identifier.uri http://hdl.handle.net/10230/58701
- dc.language.iso eng
- dc.publisher Impact Journals
- dc.relation.ispartof Oncotarget. 2017 Aug 22;8(34):56338-50
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/600388
- dc.rights All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/3.0/
- dc.subject.keyword Multiple myeloma
- dc.subject.keyword Functional screening
- dc.subject.keyword Drug sensitivity and resistance testing
- dc.subject.keyword Precision medicine
- dc.subject.keyword High-risk myeloma
- dc.title Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion