Brentuximab Vedotin for Relapsed/Refractory CD30-positive Non-Hodgkin Lymphomas
Status:
Completed
Trial end date:
2018-09-01
Target enrollment:
Participant gender:
Summary
Brentuximab vedotin is an antibody-drug conjugate targeting CD30, one of surface antigens
expressed in lymphoma cells. Fanale MA, et al. reported the results of a phase I study with
weekly dosing of brentuximab vedotin in patients with relapsed/refractory CD30-positive
hematologic malignancies (Clin Cancer Res. 2012) showed tumor regression in 85% of patients.
Thus, the overall objective response rate was 59% (24/44) including 34% (n = 14) of complete
remissions. This study mainly included Hodgkin lymphoma (n = 38) and anaplastic large cell
lymphoma (n = 5). However, its efficacy in other types of NHL has never been reported
although this study enrolled one patient with peripheral T-cell lymphoma not otherwise
specified (PTCL-NOS).
CD30 (TNFRSF8) is a transmembrane glycoprotein of the tumor necrosis factor receptor (TNFR)
superfamily, and it is involved in signal transduction via the activation of the NF-κB
pathway and the mitogen-activated protein kinases (MAPKs), ultimately modulating cell growth,
proliferation and apoptosis. CD30 is a non-lineage-specific activation marker expressed by
scattered B and T immunoblasts. In addition, a subset of cases in virtually all T-cell
lymphoma entities may also express CD30 but at variable and generally lower levels. In fact,
a recent study in 22 patients with extranodal NK/T-cell lymphoma showed 75% of positive rate
of CD30 expression (75%). Moreover, CD30 expression was also documented in the tumor sample
of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly (28.9%,
11/38). Therefore, Brentuximab vedotin may have potential benefits for patients with
CD30-positive NHL other than anaplastic large cell lymphoma such as CD30-positive PTCLs, NOS.
Considering the role of CD30 in signal transduction pathway associated with tumor growth and
proliferation, its expression may be associated with tumor aggressiveness. In accordance with
this, it is more likely that relapse or refractory NHLs may have CD30 expression, and the
potential benefits of this promising agent as a salvage therapy deserve to be further
investigated in these patients who have high risk of treatment failure. Thus, we designed a
phase II study for relapsed or refractory NHL patients. This study is to explore the safety
and activity of dosing once every 3 weeks of Brentuximab vedotin in patients with relapsed or
refractory CD30-positive NHL other than anaplastic large cell lymphoma.