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N Engl J Med. 2014 Mar 13;370(11):997-1007. doi: 10.1056/NEJMoa1315226. Epub 2014 Jan 22.

Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.

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Weill Cornell Medical College (R.R.F.), Memorial Sloan-Kettering Cancer Center (A.D.Z.), the Department of Medicine, and Columbia University Medical Center (N.L.) - all in New York; U.S. Oncology Research, Springfield, OR (J.P.S.); Stanford University School of Medicine, Stanford (S.E.C.), and Gilead Sciences, Foster City (M.A., D.M.J., L.L.M., D.L., T.M.J., R.D.D.) - both in California; Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC (B.D.C.); Fred Hutchinson Cancer Research Center, University of Washington, Seattle (J.M.P.); St. James's University Hospital, Leeds (P.H.), and Royal Liverpool University Hospital, Liverpool (A.R.P.) - both in the United Kingdom; Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York (J.C.B.); University of California San Diego, Moores Cancer Center, La Jolla (T.J.K.); Sarah Cannon Research Institute, Nashville (I.F.); Universita Vita-Salute San Raffaele, Instituto Scientifico San Raffaele, Milan (P.G.); David Geffen School of Medicine, University of California Los Angeles, Los Angeles (H.E.); Florida Cancer Specialists, Englewood (T.E.); Centre Hospitalier Lyon-Sud, Pierre-Bénite, France (B.C.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (S.M.); University of Ulm, Ulm (S.S.), and University of Cologne, Cologne (P.C., M.H.) - both in Germany; and University of Texas M.D. Anderson Cancer Center, Houston (S.M.O.).
Contributed equally



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; number, NCT01539512.).

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