Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing

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http://hdl.handle.net/10138/224250

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Majumder , M M , Silvennoinen , R , Anttila , P , Tamborero , D , Eldfors , S , Yadav , B , Karjalainen , R , Kuusanmaki , H , Lievonen , J , Parsons , A , Suvela , M , Jantunen , E , Porkka , K & Heckman , C A 2017 , ' Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing ' , Oncotarget , vol. 8 , no. 34 , pp. 56338-56350 . https://doi.org/10.18632/oncotarget.17630

Title: Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing
Author: Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmaki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Oncology
University of Helsinki, Hematologian yksikkö
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2017-08-22
Language: eng
Number of pages: 13
Belongs to series: Oncotarget
ISSN: 1949-2553
URI: http://hdl.handle.net/10138/224250
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.
Subject: multiple myeloma
functional screening
drug sensitivity and resistance testing
precision medicine
high-risk myeloma
LOW-DOSE DEXAMETHASONE
GLUCOCORTICOID-RECEPTOR
RISK-STRATIFICATION
TARGETED THERAPY
WORKING GROUP
SINGLE-AGENT
PHASE-II
CELLS
PANOBINOSTAT
COMBINATION
3122 Cancers
3111 Biomedicine
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