Certainly it seems that merely demonstrating CD30 expression does not guarantee responses to anti-CD30 therapies, as demonstrated by the disappointing results of BV in PTCL-NOS, and the recently reported failure to achieve the ORR endpoint in a phase II study of BV in primary mediastinal B-cell lymphoma, despite strong CD30 expression in this tumor type.106 Conversely, the efficacy of BV in some tumors even with low-level CD30 expression is intriguing, suggestive of off-target immune modulatory effects of the compound, as discussed earlier. This evidence concerns the gene TNFRSF8 and mature T-cell and NK-cell non-Hodgkin lymphoma.