Response to brentuximab vedotin by CD30 expression: Results from five trials in PTCL, CTCL, and B-cell lymphomas.

Abstract

7543 Background: Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, has been evaluated in multiple trials in patients (pts) with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell lymphoma. We examined the ability of CD30 expression level to predict response to BV across these patient populations. Methods: Data were integrated from 275 pts with PTCL, CTCL, and B-cell lymphoma treated with BV from 5 prospective clinical trials. Study SGN35-012 evaluated BV plus rituximab or BV monotherapy in pts with relapsed/refractory non-Hodgkin lymphoma. The ALCANZA study compared BV to physician’s choice of methotrexate or bexarotene in pts with mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL). Three investigator-sponsored trials evaluated BV monotherapy in pts with relapsed PTCL, MF, and pcALCL (35-IST-030, 35-IST-001, 35-IST-002). Exploratory analyses were conducted to examine the relationship between CD30 expression and objective response rate (ORR) for pts with CD30 expression ≥10%, <10%, or undetectable (0%) by IHC (malignant cells or lymphoid infiltrate; local review). Results: 143 pts had tumors with CD30 <10%, including 58/143 with undetectable CD30. Activity with BV was observed at all levels of CD30 expression, including CD30=0 (Table). Analysis of the interaction between CD30 and duration of response is ongoing and will be presented in the final poster. ORR by CD30 expression, n/N (%). Clinical trial information: NCT01421667, NCT02588651, NCT01578499, NCT01352520, NCT01396070. Conclusions: CD30 expression levels ≥10%, <10%, or undetectable did not predict response to BV in a range of CD30-expressing lymphomas: Clinical responses occurred in pts with CD30 low and CD30 undetectable lymphomas. Limitations of IHC, the dynamic nature and heterogeneity of cell-surface CD30 expression, and multiple mechanisms of action of BV may all contribute to this observation.[Table: see text]