title: Idelalisib for the treatment of non-Hodgkin lymphoma.
abstract: BACKGROUND
  B-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over-activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia.
  
  
  METHODS
  Herein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies.
  
  
  CONCLUSIONS
  Idelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations.
authors.affiliation: a Department of Medicine, University of Washington, Seattle , WA , USA.|b Fred Hutchinson Cancer Research Center , Seattle , WA , USA.|c Veterans Affairs Puget Sound Health Care System , Seattle , WA , USA.
authors.forename: Solomon A
authors.initials: SA
authors.lastname: Graf
authors.affiliation: a Department of Medicine, University of Washington, Seattle , WA , USA.|b Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; D000069283:Rituximab; C552946:idelalisib
keywords: B-cell; Idelalisib; indolent; lymphoma
references.citation: Blood. 2011 Sep 29;118(13):3603-12
references.pmid: 21803855
references.citation: J Oncol Pract. 2014 Jul;10(4):e208-11
references.pmid: 24803662
references.citation: J Clin Oncol. 2009 Nov 10;27(32):5404-9
references.pmid: 19805688
references.citation: Expert Rev Hematol. 2015 Dec;8(6):733-42
references.pmid: 26368831
references.citation: J Biol Chem. 2015 Mar 27;290(13):8439-46
references.pmid: 25631052
references.citation: Trends Biochem Sci. 2005 Apr;30(4):194-204
references.pmid: 15817396
references.citation: Oncotarget. 2014 Feb 28;5(4):908-15
references.pmid: 24659719
references.citation: Hematology Am Soc Hematol Educ Program. 2009;:523-31
references.pmid: 20008237
references.citation: N Engl J Med. 2014 Mar 13;370(11):997-1007
references.pmid: 24450857
references.citation: J Clin Pharmacol. 2015 Aug;55(8):909-19
references.pmid: 25760671
references.citation: Leuk Lymphoma. 2015;56(10):2779-86
references.pmid: 25726955
references.citation: Haematologica. 2015 Jan;100(1):77-86
references.pmid: 25344523
references.citation: JAMA Oncol. 2015 Jul;1(4):505-27
references.pmid: 26181261
references.citation: Blood. 2014 May 29;123(22):3398-405
references.pmid: 24615778
references.citation: J Clin Oncol. 2015 Aug 10;33(23):2516-22
references.pmid: 26124482
references.citation: J Clin Oncol. 2013 Jan 1;31(1):88-94
references.pmid: 23045577
references.citation: Ann Oncol. 2015 Aug;26(8):1667-77
references.pmid: 25712458
references.citation: Blood Cancer J. 2014 Oct 17;4:e251
references.pmid: 25325301
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1570-5
references.pmid: 17353550
references.citation: Blood. 2015 Apr 2;125(14):2306-9
references.pmid: 25838279
references.citation: Clin Cancer Res. 2009 Jan 1;15(1):355-60
references.pmid: 19118065
references.citation: Clin Adv Hematol Oncol. 2014 Feb;12(2 Suppl 6):8-9
references.pmid: 24870874
references.citation: Blood. 2015 Dec 17;126(25):2686-94
references.pmid: 26472751
references.citation: Lancet Oncol. 2011 Aug;12(8):773-84
references.pmid: 21724462
references.citation: J Biol Chem. 1997 Aug 1;272(31):19236-41
references.pmid: 9235916
references.citation: Clin Pharmacokinet. 2016 Jan;55(1):33-45
references.pmid: 26242379
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1209-13
references.pmid: 19188674
references.citation: Cell Death Dis. 2015 Jan 15;6:e1593
references.pmid: 25590803
references.citation: Cancer Chemother Pharmacol. 2015 Dec;76(6):1133-41
references.pmid: 26526983
references.citation: J Clin Oncol. 2012 Aug 10;30(23):2820-2
references.pmid: 22778323
references.citation: Leuk Lymphoma. 2015;56(10):2834-40
references.pmid: 25669927
references.citation: JAMA Oncol. 2015 Apr;1(1):80-7
references.pmid: 26182309
references.citation: Leuk Lymphoma. 2015;56(12):3393-400
references.pmid: 26237681
references.citation: Clin Cancer Res. 2015 Apr 1;21(7):1525-9
references.pmid: 25645861
references.citation: Cancer Treat Res. 2015;165:197-226
references.pmid: 25655611
references.citation: Blood. 2011 Jan 13;117(2):591-4
references.pmid: 20959606
references.citation: Hematology Am Soc Hematol Educ Program. 2013;2013:553-60
references.pmid: 24319231
references.citation: N Engl J Med. 2014 Mar 13;370(11):1008-18
references.pmid: 24450858
references.citation: Blood. 2015 May 21;125(21):3357-9
references.pmid: 25999447
references.citation: J Clin Pharmacol. 2015 Aug;55(8):944-52
references.pmid: 25821156
references.citation: N Engl J Med. 2014 Mar 20;370(12):1101-10
references.pmid: 24401022
references.citation: Blood. 2011 Mar 10;117(10):2807-12
references.pmid: 21239695
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4330-5
references.pmid: 9113989
references.citation: J Oncol Pract. 2015 May;11(3):252-8
references.pmid: 25804983
references.citation: Blood. 2014 May 29;123(22):3390-7
references.pmid: 24615777
references.citation: Am J Hematol. 2010 Sep;85(9):670-4
references.pmid: 20652865
references.citation: J Clin Oncol. 2012 Nov 1;30(31):3848-53
references.pmid: 23008294
references.citation: Leukemia. 2014 Nov;28(11):2188-96
references.pmid: 24699307
references.citation: Blood. 2010 Sep 23;116(12):2078-88
references.pmid: 20522708
references.citation: Blood. 2014 May 29;123(22):3406-13
references.pmid: 24615776
references.citation: Lancet Oncol. 2014 Nov;15(12):1311-8
references.pmid: 25439689
references.citation: Lancet. 2015 May 9;385(9980):1873-83
references.pmid: 25882396
references.citation: Blood. 2010 Apr 1;115(13):2578-85
references.pmid: 19965662