title: Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression.
abstract: Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jacobsen
authors.affiliation: Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR;
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Sharman
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Stanford University Medical Center, Stanford, CA;
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: Northwestern University, Chicago, IL;
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL;
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Bello
authors.affiliation: St. Francis Hospital, Upstate Oncology Associates, Greenville, SC;
authors.forename: Gary
authors.initials: G
authors.lastname: Spitzer
authors.affiliation: Seattle Genetics, Inc., Bothell, WA; and.
authors.forename: Maria Corinna
authors.initials: MC
authors.lastname: Palanca-Wessels
authors.affiliation: Seattle Genetics, Inc., Bothell, WA; and.
authors.forename: Dana A
authors.initials: DA
authors.lastname: Kennedy
authors.affiliation: Seattle Genetics, Inc., Bothell, WA; and.
authors.forename: Pamela
authors.initials: P
authors.lastname: Levine
authors.affiliation: Seattle Genetics, Inc., Bothell, WA; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Washington University School of Medicine, St. Louis, MO.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000079963:Brentuximab Vedotin; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D017730:Ki-1 Antigen / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin