Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry

Leuk Lymphoma. 2017 Jul;58(7):1607-1616. doi: 10.1080/10428194.2016.1256481. Epub 2016 Nov 20.

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).

Keywords: DLBCL; antibody-based immunotherapy; antibody-drug conjugate; immunotherapy; lymphoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Brentuximab Vedotin
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / adverse effects
  • Immunoconjugates / therapeutic use*
  • Immunohistochemistry
  • Ki-1 Antigen / metabolism
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Recurrence
  • Retreatment
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers
  • Immunoconjugates
  • Ki-1 Antigen
  • Brentuximab Vedotin

Associated data

  • ClinicalTrials.gov/NCT01421667