Ontology highlight
ABSTRACT: Objectives
In the TOURMALINE-MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib-lenalidomide-dexamethasone (IRd) showed different magnitudes of progression-free survival (PFS) benefit vs placebo-Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT).Methods
RNA sequencing data were used to investigate the basis of these differences.Results
The PFS benefit of IRd vs placebo-Rd was greater in patients with tumors expressing high c-MYC levels (median not reached vs 11.3 months; hazard ratio [HR] 0.42; 95% CI, 0.26, 0.66; P < .001) compared with in those expressing low c-MYC levels (median 20.6 vs 16.6 months; HR 0.75; 95% CI, 0.42, 1.2). Expression of c-MYC in tumors varied based on the number and type of prior therapy received, with the lowest levels observed in tumors of patients who had received 1 prior line of therapy including SCT. These tumors also had higher expression levels of CD19 and CD81.Conclusions
PFS analyses suggest that lenalidomide and ixazomib target tumors with different levels of c-MYC, CD19, and CD81 expression, thus providing a potential rationale for the differential benefits observed in the TOURMALINE-MM1 study. This trial was registered at www.clinicaltrials.gov as: NCT01564537.
SUBMITTER: Di Bacco A
PROVIDER: S-EPMC7317705 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Di Bacco Alessandra A Bahlis Nizar J NJ Munshi Nikhil C NC Avet-Loiseau Hervé H Masszi Tamás T Viterbo Luísa L Pour Ludek L Ganly Peter P Cavo Michele M Langer Christian C Kumar Shaji K SK Rajkumar S Vincent SV Keats Jonathan J JJ Berg Deborah D Lin Jianchang J Li Bin B Badola Sunita S Shen Lei L Zhang Jacob J Esseltine Dixie-Lee DL Luptakova Katarina K van de Velde Helgi H Richardson Paul G PG Moreau Philippe P
European journal of haematology 20200415 1
<h4>Objectives</h4>In the TOURMALINE-MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib-lenalidomide-dexamethasone (IRd) showed different magnitudes of progression-free survival (PFS) benefit vs placebo-Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT).<h4>Methods</h4>RNA sequencing data were used to investigate the basis of these differences.< ...[more]