Brentuximab Vedotin Shows First-Line Activity in Phase I Study in CD30-Positive Peripheral T-Cell Lymphoma
In a phase I study reported in the Journal of Clinical Oncology, Fanale et al found that brentuximab vedotin (Adcetris)—a conjugate of antibody specific for CD30 and a microtubule-disrupting chemotherapy agent—exhibited high activity when combined sequentially with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or concurrently with CHP (CHOP without vincristine) in front-line treatment of peripheral T-cell lymphoma. Treatment had a manageable toxicity profile.
Study Details
In the study, patients with systemic anaplastic large-cell lymphoma received sequential treatment with brentuximab vedotin at 1.8 mg/kg (two cycles) followed by CHOP (six cycles) every 3 weeks and patients with peripheral T-cell lymphoma including those with systemic anaplastic large-cell lymphoma received concurrent brentuximab vedotin at 1.8 mg/kg plus CHP for six cycles every 3 weeks. Responders received single-agent brentuximab vedotin for 8 to 10 additional cycles. Both ALK-positive and ALK-negative patients were included.
Response Rates
Objective response was observed in 11 (85%) of 13 patients receiving sequential treatment, with complete response observed in 62%, and estimated 1-year progression-free survival was 77%. Enrolment in the sequential group was stopped after observation of disease recurrence during CHOP in patients with initial response to brentuximab vedotin.
Objective response was observed in 26 (100%) of 26 patients receiving concurrent treatment, with complete response observed in 88%, and estimated 1-year progression-free survival was 71%. Response was observed in each of seven patients without systemic anaplastic large-cell lymphoma.
Toxicity
Grade 3 or 4 febrile neutropenia, neutropenia, anemia, peripheral sensory neuropathy, constipation, and fatigue each occurred in 15% of patients receiving sequential therapy. The most common grade 3 or 4 adverse events in those receiving concurrent therapy were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).
The investigators concluded: “Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30+ [peripheral T-cell lymphoma]. A randomized phase III trial is under way, comparing [brentuximab vedotin plus] CHP with CHOP (clinical trial No. NCT01777152).
Michelle A. Fanale, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Supported by a National Cancer Institute grant and by Seattle Genetics and Takeda Pharmaceuticals International. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
