A phase II, open-label study evaluating the efficacy of brentuximab vedotin (Adcetris), an anti-CD antibody-drug conjugate, found that among 48 evaluable patients with CD30-positive diffuse large B-cell lymphoma (DLBCL), 21 (44%) had objective responses. These responses included 8 patients (17%) with complete remission and 13 (27%) with partial remission. “Complete remissions were durable, with a median duration of 16.6 months,” Eric D. Jacobsen, MD, of Dana-Farber Cancer Institute, Boston, and colleagues reported in Blood.
The planned subset analysis of B-cell non-Hodgkin lymphomas (NHL) also included 19 patients with other B-cell NHLs. The median ages were 62 among patients with DLBCL and 36 among patients with other B-cell lymphomas.
“Patients could have any subtype of histologically confirmed B-cell lymphoma with detectable CD30 expression by visual assessment of immunohistochemistry,” according to the study report. “All eligible patients had bidimensionally measurable disease of 1.5 cm in greatest transverse diameter and no history of another active invasive malignancy within the previous 3 years.” Most patients had stage III or IV disease. More than half of all patients had received at least three prior systemic therapies, and nearly all had received prior rituximab (Rituxan).
All patients received 1.8 mg/kg of brentuximab vedotin IV every 3 weeks, and those achieving stable disease or better could receive continued treatment until disease progression, unacceptable toxicity, or study closure. To assess the safety of brentuximab vedotin when given in combination with rituximab, a separate cohort of patients (planned n ≈ 15) received brentuximab vedotin (1.8 mg/kg IV) in combination with rituximab (375 mg/m2) on day 1 of each 3-week cycle. Patients were treated at 26 sites in the United States.
“DLBCL patients were generally refractory to front-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% complete remission),” the investigators noted. Responses occurred across a range of CD30 expression. “To further understand the activity of brentuximab vedotin in patients with low levels of CD30 expression, this study was amended in July 2013 to evaluate the efficacy of monotherapy in DLBCL patients with undetectable CD30 expression by visual assessment of immunohistochemistry. Results from this cohort are forthcoming.
“There was no correlation between response and level of CD30 expression,” the authors noted.
Among patients with other B-cell lymphomas, there was one complete remission and two partial remissions among six patients with gray zone NHL, one complete remission among six patients with primary mediastinal B-cell lymphoma, and one complete remission among three patients with post-transplant lymphoproliferative disorder.
“Brentuximab vedotin as a single agent and in combination with rituximab was generally well tolerated in these heavily pretreated patients with advanced disease,” the investigators noted, with adverse events consistent with known toxicities. Treatment-emergent adverse events occurring in at least 25% of B-cell patients treated with single-agent brentuximab vedotin included fatigue, diarrhea, neutropenia, nausea, decreased appetite, pyrexia, and peripheral sensory neuropathy. “All five deaths within 30 days of the last study treatment were disease related,” the authors stated. ■
Jacobsen ED, et al: Blood 125:1394-1402, 2015.