Universität zu Köln

Furman, Richard R., Sharman, Jeff P., Coutre, Steven E., Cheson, Bruce D., Pagel, John M., Hillmen, Peter, Barrientos, Jacqueline C., Zelenetz, Andrew D., Kipps, Thomas J., Flinn, Ian ORCID: 0000-0001-6724-290X, Ghia, Paolo ORCID: 0000-0003-3750-7342, Eradat, Herbert, Ervin, Thomas, Lamanna, Nicole ORCID: 0000-0003-3331-9491, Coiffier, Bertrand, Pettitt, Andrew R., Ma, Shuo, Stilgenbauer, Stephan, Cramer, Paula, Aiello, Maria, Johnson, Dave M., Miller, Langdon L., Li, Daniel, Jahn, Thomas M., Dansey, Roger D., Hallek, Michael and O'Brien, Susan M. (2014). Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N. Engl. J. Med., 370 (11). S. 997 - 1008. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

BackgroundPatients 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. MethodsIn 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. ResultsThe 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. ConclusionsThe 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.) A placebo-controlled study of idelalisib in patients with relapsed chronic lymphocytic leukemia who were receiving rituximab was stopped early because of significant improvement in rates of response, progression-free survival, and overall survival with idelalisib. Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Standard treatments include combinations of purine analogues, alkylating agents, and monoclonal antibodies. In younger patients without major coexisting illnesses, these regimens can provide high response rates of durable length but have substantial toxic effects. As a result, these treatments often have unacceptable side effects in older patients and those with coexisting illnesses.(1) Patients with relapsed CLL often have limited options because of the development of resistance to, or persisting toxic effects of, previous therapies. This is particularly true for elderly patients and those with coexisting illnesses.(2) For these patients, ...

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Furman, Richard R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sharman, Jeff P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Coutre, Steven E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cheson, Bruce D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pagel, John M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmen, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Barrientos, Jacqueline C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zelenetz, Andrew D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kipps, Thomas J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Flinn, Ian UNSPECIFIED orcid.org/0000-0001-6724-290X UNSPECIFIED Ghia, Paolo UNSPECIFIED orcid.org/0000-0003-3750-7342 UNSPECIFIED Eradat, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Ervin, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Lamanna, Nicole UNSPECIFIED orcid.org/0000-0003-3331-9491 UNSPECIFIED Coiffier, Bertrand UNSPECIFIED UNSPECIFIED UNSPECIFIED Pettitt, Andrew R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ma, Shuo UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Cramer, Paula UNSPECIFIED UNSPECIFIED UNSPECIFIED Aiello, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnson, Dave M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Langdon L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Jahn, Thomas M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dansey, Roger D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Brien, Susan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443423
DOI:	10.1056/NEJMoa1315226
Journal or Publication Title:	N. Engl. J. Med.
Volume:	370
Number:	11
Page Range:	S. 997 - 1008
Date:	2014
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOMIC ABERRATIONS; SURVIVAL; INHIBITOR; EXPRESSION; CAL-101; MUTATION; DISEASE; PI3K Multiple languages Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44342