Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.
N Engl J Med
; 370(11): 997-1007, 2014 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-24450857
ABSTRACT
BACKGROUND:
Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population.METHODS:
In this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. The primary end point was progression-free survival. At the first prespecified interim analysis, the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy.RESULTS:
The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death in the idelalisib group, 0.15; P<0.001). Patients receiving idelalisib versus those receiving placebo had improved rates of overall response (81% vs. 13%; odds ratio, 29.92; P<0.001) and overall survival at 12 months (92% vs. 80%; hazard ratio for death, 0.28; P=0.02). Serious adverse events occurred in 40% of the patients receiving idelalisib and rituximab and in 35% of those receiving placebo and rituximab.CONCLUSIONS:
The combination of idelalisib and rituximab, as compared with placebo and rituximab, significantly improved progression-free survival, response rate, and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy. (Funded by Gilead; ClinicalTrials.gov number, NCT01539512.).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Purinas
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Leucemia Linfocítica Crônica de Células B
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Protocolos de Quimioterapia Combinada Antineoplásica
/
Quinazolinonas
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Anticorpos Monoclonais Murinos
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
N Engl J Med
Ano de publicação:
2014
Tipo de documento:
Article