title: Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry.
abstract: This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing DLBCL; after several patients with little to no CD30 achieved a complete remission (CR), the study evaluated treatment of DLBCL with undetectable CD30 (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL patients (31%) had an objective response (6 CRs [12%]). Median progression-free survival (PFS) was 1.4 months (range, 0.4-15.6) and median overall survival (OS) was 7.5 months (range, 0.7-18.6+). Subsequent CD30 expression quantitated by computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL responders had ≥1% CD30. Correlative analyses of CD30u and CD30-expressing DLBCL combined demonstrated that ≥1% CD30 expression by cIHC resulted in a trend toward a higher response rate and significantly longer median PFS and OS. A minimum CD30 expression threshold appears to be required for antitumor activity in DLBCL; however, other factors also likely contribute to activity. (NCT01421667).
authors.affiliation: a Department of Medicine, Oncology Division, Medical Oncology, Washington University School of Medicine , St. Louis , MO , USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.affiliation: b Hematology and Oncology, The Cleveland Clinic , Cleveland , OH , USA.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: c Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center , Duarte , CA , USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Siddiqi
authors.affiliation: d Medicine ? Oncology, Stanford University Medical Center , Stanford , CA , USA.
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: e Medicine and Experimental Therapeutics, Columbia University Medical Center/New York Presbyterian Hospital , New York , NY , USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.affiliation: f Medical Oncology ? Hematology Research, Willamette Valley Cancer Institute and Research Center/US Oncology Research , Eugene , OR , USA.
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Sharman
authors.affiliation: g Oncology ? Lymphoma Division, Hackensack University Medical Center , Hackensack , NJ , USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.affiliation: h Centre for Lymphoid Cancer, British Columbia Cancer Agency , Vancouver , BC , Canada.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Savage
authors.affiliation: i Division of Hematology, Seattle Cancer Care Alliance/University of Washington Medical Center , Seattle , WA , USA.
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Shustov
authors.affiliation: j Department of Medicine, New York University Langone Medical Center , New York , NY , USA.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Diefenbach
authors.affiliation: k Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: l Clinical Development, Seattle Genetics, Inc. , Bothell , WA , USA.
authors.forename: Maria Corinna
authors.initials: MC
authors.lastname: Palanca-Wessels
authors.affiliation: m Biostatistics, Seattle Genetics, Inc. , Bothell , MA , USA.
authors.forename: Mayur
authors.initials: M
authors.lastname: Uttarwar
authors.affiliation: n Diagnostics & Biomarkers, Seattle Genetics, Inc. , Bothell , MA , USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Li
authors.affiliation: o Clinical Pharmacology, Seattle Genetics, Inc. , Bothell , MA , USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: p Hematologic Oncology, Dana-Farber Cancer Institute , Boston , MA , USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jacobsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D000079963:Brentuximab Vedotin; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D015415:Biomarkers; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin
keywords: DLBCL; antibody-based immunotherapy; antibody-drug conjugate; immunotherapy; lymphoma