Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral t-cell lymphomas: Results of a phase i study

Michelle A. Fanale, Steven M. Horwitz, Andres Forero-Torres, Nancy L. Bartlett, Ranjana H. Advani, Barbara Pro, Robert W. Chen, Andrew Davies, Tim Illidge, Dirk Huebner, Dana A. Kennedy, Andrei R. Shustov

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

Purpose: Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30+ PTCL.

Patients and Methods: Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prspecified comparisons of the two treatment approaches.

Results: After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n=26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (+ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).

Conclusion: 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+ PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152).

Original languageEnglish
Pages (from-to)3137-3143
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number28
DOIs
StatePublished - Oct 1 2014

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