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.

• Klíčová slova
• RNA sequencing, c-myc Proto-Oncogenes, multiple myeloma, mutation, progression-free survival,
• MeSH
• dexamethason MeSH
• doba přežití bez progrese choroby MeSH
• exprese genu * MeSH
• glycin analogy a deriváty   MeSH
• lenalidomid MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   genetika   mortalita   patologie   MeSH
• nádorové biomarkery MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• protoonkogenní proteiny c-myc genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sloučeniny boru MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese MeSH
• stupeň nádoru MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dexamethason MeSH
• glycin MeSH
• ixazomib MeSH Prohlížeč
• lenalidomid MeSH
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-myc MeSH
• sloučeniny boru MeSH