Chapman, MA;
Sive, J;
Ambrose, J;
Roddie, C;
Counsell, N;
Lach, A;
Abbasian, M;
... Yong, K; + view all
(2018)
RNA-Seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature.
Blood
, 132
(20)
pp. 2154-2165.
10.1182/blood-2018-05-849893.
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Yong_RNA seq of newly diagnosed patients in the padimac study leads to a bortezomib or lenalidomide decision signature_AAM.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Improving outcomes in multiple myeloma will not only involve development of new therapies, but better use of existing treatments. We performed RNA sequencing (RNA-Seq) on samples from newly diagnosed patients enrolled into the phase II PADIMAC (Bortezomib, Adriamycin, and Dexamethasone (PAD) Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease (MRD) in Patients with Deferred ASCT) study. Using synthetic annealing and the Large-Margin-Nearest-Neighbor algorithm, we developed and trained a seven-gene signature to predict treatment outcome. We tested the signature on independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass (relating Clinical outcomes in Multiple Myeloma to personal assessment of genetic profile) dataset, patients who were treated correctly according to the signature had a better progression-free survival (median 20.1 months versus not reached; hazard ratio 0.40; confidence interval 0.23-0.72; p=0.0012) and overall survival (median 30.7 months versus not reached; hazard ratio 0.41; confidence interval 0.21-0.80; p=0.0049) than those who were not. Indeed, the outcome for these correctly treated patients was non-inferior to those treated with combined bortezomib, lenalidomide, and dexamethasone, arguably the standard of care in the United States, but not widely available elsewhere. The small size of the signature will facilitate clinical translation, thus enabling more targeted drug regimens to be delivered in myeloma.
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