Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study

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 prespecified 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).

Trial registration: ClinicalTrials.gov NCT01309789 NCT01777152 NCT01309789.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

© 2014 by American Society of Clinical Oncology.

Figures

Fig 1.

Progression-free survival by Kaplan-Meier analysis for patients receiving combination treatment. Eleven patients experienced progressive disease or death after a median observation time of 21.4 months. Median progression-free survival was not reached (95% CI, 11.7 to NE). Circles on the plot indicate censored patients. Shaded area indicates the 95% CIs. NE, not estimable.

Fig A1.

Study schema showing screening, study treatment, and end of treatment for the sequential and combination treatment approaches. Sequential treatment included brentuximab vedotin (BV; two cycles) followed by cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP; six cycles). The combination-treatment approach involved treatment with BV plus CHOP without vincristine (CHP; six cycles) and included a cohort to evaluate any dose-limiting toxicities (DLT; and the maximum-tolerated dose) during cycle 1. Responding patients were eligible to receive subsequent single-agent brentuximab vedotin for eight cycles (sequential treatment) or 10 cycles (combination treatment). During the follow-up period, after receiving the last dose of the study drug, patients were assessed for survival and disease status every 3 months until death or study closure.

Fig A2.

Progression-free survival among patients receiving sequential treatment by Kaplan-Meier analysis. Six patients experienced progressive disease or death after a median observation time of 23.8 months. Median progression-free survival was 22.1 months (95% CI, 8.8 to not estimable [NE]). Circles on the plot indicate censored patients. Shaded area indicates 95% CIs.

Fig A3.

Overall survival among patients receiving (A) sequential treatment or (B) combination treatment by Kaplan-Meier analysis. Three patients receiving sequential treatment died after a median observation time of 23.8 months. Among patients receiving combination treatment, five patients died after a median observation time of 21.4 months. Median overall survival was not reached estimable (NE) for either treatment approach. Circles on the plots indicate censored patients. Shaded areas indicate 95% CIs.