Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. Academic Article Article uri icon

Overview

MeSH

  • Aged
  • Aged, 80 and over
  • Class Ia Phosphatidylinositol 3-Kinase
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Diseases
  • Lymph Nodes
  • Male
  • Middle Aged
  • Recurrence
  • Rituximab

MeSH Major

  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Purines
  • Quinazolinones

abstract

  • 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. 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. 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. 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.).

publication date

  • March 13, 2014

has subject area

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols
  • Class Ia Phosphatidylinositol 3-Kinase
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Diseases
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymph Nodes
  • Male
  • Middle Aged
  • Purines
  • Quinazolinones
  • Recurrence
  • Rituximab

Research

keywords

  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

Identity

Language

  • eng

PubMed Central ID

  • PMC4161365

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1315226

PubMed ID

  • 24450857

Additional Document Info

start page

  • 997

end page

  • 1007

volume

  • 370

number

  • 11