RNA-Seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature

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 study. Using an empirical Bayes approach and synthetic annealing, 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 dataset, patients who were treated correctly according to the signature had a better progression-free and overall survival 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 (VRD). 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 (autologous stem cell transplant) Overall design: RNA-Seq data from 44 patients enrolled into the PADIMAC study who provided RNA with an RNA Integrity score of 6 or greater. Thirteen out of forty-four patients had at least a very good partial remission sustained for at least a year without progression and were labelled as "bortezomib-good".

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Chapman MA, Sive J, Ambrose J, Roddie C, Counsell N, Lach A, Abbasian M, Popat R, Cavenagh JD, Oakervee H, Streetly MJ, Schey S, Koh M, Willis F, Virchis AE, Crowe J, Quinn MF, Cook G, Crawley CR, Pratt G, Cook M, Braganza N, Adedayo T, Smith P, Clifton-Hadley L, Owen RG, Sonneveld P, Keats JJ, Herrero J, Yong K