title: R-CHOP with iodine-131 tositumomab consolidation for advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0433.
abstract: Radiolabelled antiCD-20 antibodies have demonstrated single agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). The S0433 clinical trial enrolled patients with newly diagnosed, advanced stage or bulky stage II, histologically confirmed DLBCL. Patients received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles of CHOP, then iodine-131 tositumomab radioimmunotherapy consolidation 30-60 d after completion of chemotherapy. The primary endpoint was 2-year progression-free survival (PFS). Eighty-four eligible patients were enrolled, and 56 patients completed the entire course of protocol treatment. Of the 84 patients evaluable for treatment response, 72 [86%, 95% confidence interval (CI): 76-92%] achieved a partial response (n = 21) or a confirmed (n = 41) or unconfirmed (n = 10) complete response to therapy. With a median follow-up of 3·9 years, the 2-year PFS estimate is 69% and the 2-year overall survival estimate is 77%. Rituximab levels at time of radioimmunotherapy did not correlate with toxicity or outcome. Twenty percent of patients had double hit features (MYC+; BCL2+) by immunohistochemistry, and had inferior outcome. These current results suggest that the incorporation of novel agents earlier in therapy may ultimately have greater impact in DLBCL, as early progressions, deaths and declining performance status during CHOP chemotherapy limited the number of patients who ultimately could benefit from radioimmunotherapy consolidation.
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Unger
authors.forename: W Richard
authors.initials: WR
authors.lastname: Burack
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Robert N
authors.initials: RN
authors.lastname: Raju
authors.forename: Auayporn P
authors.initials: AP
authors.lastname: Nademanee
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016499:Radioimmunotherapy; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C119496:tositumomab I-131; D011241:Prednisone
keywords: chemotherapeutic approaches; diffuse large B cell lymphoma; lymphoma; pharmacotherapeutics; radioimmunotherapy
references.citation: Ann Oncol. 2008 Apr;19(4):769-73
references.pmid: 18303033
references.citation: J Clin Oncol. 2005 Jun 20;23(18):4117-26
references.pmid: 15867204
references.citation: Semin Hematol. 2008 Apr;45(2):110-7
references.pmid: 18381106
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3439-43
references.pmid: 22949152
references.citation: J Clin Oncol. 2013 Jan 20;31(3):314-20
references.pmid: 23233710
references.citation: J Clin Oncol. 2010 Aug 10;28(23):3709-16
references.pmid: 20625137
references.citation: Lancet Oncol. 2008 Feb;9(2):105-16
references.pmid: 18226581
references.citation: J Clin Oncol. 2013 May 1;31(13):1662-8
references.pmid: 23478060
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3460-7
references.pmid: 22665537
references.citation: J Clin Oncol. 1983 Nov;1(11):710-9
references.pmid: 6668489
references.citation: J Clin Oncol. 1999 Apr;17(4):1244
references.pmid: 10561185
references.citation: Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5598s-5603s
references.pmid: 17875795
references.citation: N Engl J Med. 2008 Nov 27;359(22):2313-23
references.pmid: 19038878
references.citation: Ann Oncol. 2008 May;19(5):964-9
references.pmid: 18296419
references.citation: N Engl J Med. 2002 Jan 24;346(4):235-42
references.pmid: 11807147
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3433-5
references.pmid: 22949148
references.citation: Clin Cancer Res. 2011 Oct 1;17(19):6112-7
references.pmid: 21844008
references.citation: Blood. 2007 Jul 1;110(1):54-8
references.pmid: 17387223
references.citation: Blood. 2003 Sep 1;102(5):1606-12
references.pmid: 12738671
references.citation: Br J Haematol. 2009 Aug;146(3):282-91
references.pmid: 19519691
references.citation: Clin Cancer Res. 2010 Aug 1;16(15):3998-4004
references.pmid: 20542986
references.citation: Lancet Oncol. 2006 May;7(5):379-91
references.pmid: 16648042
references.citation: Haematologica. 2013 Nov;98(11):1732-8
references.pmid: 23812930
references.citation: N Engl J Med. 2013 Oct 31;369(18):1681-90
references.pmid: 24171516
references.citation: Blood. 2005 Jan 15;105(2):489-95
references.pmid: 15358617
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3452-9
references.pmid: 22851565
references.citation: J Clin Oncol. 2006 Sep 1;24(25):4143-9
references.pmid: 16896003
references.citation: Am J Hematol. 2013 Jul;88(7):589-93
references.pmid: 23619698
references.citation: Blood. 2004 Jan 1;103(1):275-82
references.pmid: 14504078
references.citation: J Clin Oncol. 2010 May 10;28(14):2373-80
references.pmid: 20385988
references.citation: Blood. 2008 Aug 1;112(3):830-5
references.pmid: 18502830