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

被引:36
作者
Majumder, Muntasir Mamun [1 ]
Silvennoinen, Raija [2 ,3 ]
Anttila, Pekka [3 ]
Tamborero, David [4 ]
Eldfors, Samuli [1 ]
Yadav, Bhagwan [1 ]
Karjalainen, Riikka [1 ]
Kuusanmaki, Heikki [1 ]
Lievonen, Juha [3 ]
Parsons, Alun [1 ]
Suvela, Minna [1 ]
Jantunen, Esa [2 ]
Porkka, Kimmo [3 ,5 ]
Heckman, Caroline A. [1 ]
机构
[1] Univ Helsinki, Inst Mol Med Finland, Helsinki Inst Life Sci, Helsinki, Finland
[2] Kuopio Univ Hosp, Dept Med, Kuopio, Finland
[3] Helsinki Univ Hosp, Dept Hematol, Comprehens Canc Ctr, Helsinki, Finland
[4] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona, Spain
[5] Univ Helsinki, Hematol Res Unit, Helsinki, Finland
关键词
multiple myeloma; functional screening; drug sensitivity and resistance testing; precision medicine; high-risk myeloma; GLUCOCORTICOID-RECEPTOR; RISK-STRATIFICATION; SINGLE-AGENT; PHASE-II; PANOBINOSTAT; COMBINATION; BORTEZOMIB; DOVITINIB; HETEROGENEITY; DEXAMETHASONE;
D O I
10.18632/oncotarget.17630
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:56338 / 56350
页数:13
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