Idelalisib and rituximab in relapsed chronic lymphocytic leukemia

Richard R. Furman*, Jeff P. Sharman, Steven E. Coutre, Bruce D. Cheson, John M. Pagel, Peter Hillmen, Jacqueline C. Barrientos, Andrew D. Zelenetz, Thomas J. Kipps, Ian Flinn, Paolo Ghia, Herbert Eradat, Thomas Ervin, Nicole Lamanna, Bertrand Coiffier, Andrew R. Pettitt, Shuo Ma, Stephan Stilgenbauer, Paula Cramer, Maria AielloDave M. Johnson, Langdon L. Miller, Daniel Li, Thomas M. Jahn, Roger D. Dansey, Michael Hallek, Susan M. O'Brien

*Corresponding author for this work

Research output: Contribution to journalArticle

1103 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)997-1007
Number of pages11
JournalNew England Journal of Medicine
Volume370
Issue number11
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Idelalisib and rituximab in relapsed chronic lymphocytic leukemia'. Together they form a unique fingerprint.

  • Cite this

    Furman, R. R., Sharman, J. P., Coutre, S. E., Cheson, B. D., Pagel, J. M., Hillmen, P., Barrientos, J. C., Zelenetz, A. D., Kipps, T. J., Flinn, I., Ghia, P., Eradat, H., Ervin, T., Lamanna, N., Coiffier, B., Pettitt, A. R., Ma, S., Stilgenbauer, S., Cramer, P., ... O'Brien, S. M. (2014). Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. New England Journal of Medicine, 370(11), 997-1007. https://doi.org/10.1056/NEJMoa1315226