Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia.
Furman, Richard R. M.D.; Sharman, Jeff P. M.D.; Coutre, Steven E. M.D.; Cheson, Bruce D. M.D.; Pagel, John M. M.D., Ph.D.; Hillmen, Peter M.B., Ch.B., Ph.D.; Barrientos, Jacqueline C. M.D.; Zelenetz, Andrew D. M.D., Ph.D.; Kipps, Thomas J. M.D., Ph.D.; Flinn, Ian M.D., Ph.D.; Ghia, Paolo M.D., Ph.D.; Eradat, Herbert M.D.; Ervin, Thomas M.D.; Lamanna, Nicole M.D.; Coiffier, Bertrand M.D., Ph.D.; Pettitt, Andrew R. Ph.D., F.R.C.Path.; Ma, Shuo M.D., Ph.D.; Stilgenbauer, Stephan M.D.; Cramer, Paula M.D.; Aiello, Maria M.A.; Johnson, Dave M. B.S.; Miller, Langdon L. M.D.; Li, Daniel Ph.D.; Jahn, Thomas M. M.D., Ph.D.; Dansey, Roger D. M.D.; Hallek, Michael M.D.; O'Brien, Susan M. M.D.
[Article]
New England Journal of Medicine.
370(11):997-1007, March 13, 2014.
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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.)
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