Credit: Linda Bartlett
NEW ORLEANS—Brentuximab vedotin has demonstrated “compelling” antitumor activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.
The investigators were also surprised
to find that the activity of this anti-CD30 monoclonal antibody
conjugate did not seem to
correlate with a patient’s level of CD30 expression.
In fact, some of
the patients with the weakest CD30 expression had the best responses to
the drug.
Eric Jacobsen, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues presented these results at the 2013 ASH Annual Meeting as abstract 848.
Thus far, the researchers have enrolled 62 patients with B-cell lymphomas, including 44 with DLBCL, on this phase 2 study.
Sixty-five percent of patients had primary refractory disease, 76% were refractory to their most recent prior therapy, and 23% had never responded to any treatment.
However, 40% of the 43 evaluable DLBCL patients had an objective response to brentuximab vedotin. The median response duration was 36 weeks, and some responses lasted more than 8 months.
Seven patients had complete remissions, and 10 had partial remissions. In the other B-cell lymphoma patients, 22 had an objective response.
The researchers called this compelling antitumor activity in a highly refractory population.
“[Brentuximab vedotin] was more active than many expected,” Dr Jacobsen said. “In my opinion, these results are encouraging enough to take the drug forward in diffuse large B-cell lymphoma.”
The researchers said the drug’s safety profile was consistent with previous results. Six patients stopped treatment due to adverse events, including 2 who developed peripheral neuropathy.
Treatment-emergent adverse events included fatigue (40%), nausea (37%), neutropenia (37%), fever (32%), diarrhea (31%), peripheral sensory neuropathy (26%), vomiting (23%), anemia (21%), and constipation (21%).
Role of CD30
Brentuximab vedotin is a monoclonal antibody that binds to CD30. This molecule’s expression varies, but researchers have estimated that CD30 is present in a quarter to a third of B-cell non-Hodgkin lymphoma cells.
In this study, some of the patients’ lymphoma cells strongly expressed CD30. But, in other patients, the investigators were unable to detect any CD30 expression at all. And the patients’ level of CD30 expression bore no relationship to how they responded to the drug.
“In fact, although the trend was not statistically significant, there was almost an inverse correlation,” Dr Jacobsen said. “Some patients with the weakest CD30 expression had the most positive responses.”
One possible explanation for this is that the drug bound to another target, but preclinical tests suggested this was not the case. Other possibilities are that brentuximab vedotin binds more effectively to CD30 than the antibody used to detect CD30 in the lab or that different cells have differing abilities to ingest brentuximab once the antibody binds to the cell.
There is no clear answer from the study, Dr Jacobsen said, but lab tests are ongoing. He and his colleagues are beginning to evaluate the drug’s activity in a cohort of patients whose lymphomas have no measurable CD30 expression.
This study was supported by Seattle Genetics.
