c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma.
Eur J Haematol
; 105(1): 35-46, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32145111
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
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Proteínas Proto-Oncogênicas c-myc
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Mieloma Múltiplo
Tipo de estudo:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Haematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos