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 ( MabThera, Rituxan ) versus Rituximab plus placebo.
Researchers have 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 less than 0.001 ).
Patients receiving Idelalisib versus those receiving placebo had improved rates of overall response ( 81% vs 13%; odds ratio, 29.92; P less than 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.
In conclusion, 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 chronic lymphocytic leukemia who were less able to undergo chemotherapy. ( Xagena )
Furman RR et al, N Engl J Med 2014; 370:997-1007