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).

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 28 Pg. 3137-43 (Oct 01 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25135998 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Immunoconjugates
• Ki-1 Antigen
• Vincristine
• Brentuximab Vedotin
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Brentuximab Vedotin
• Cyclophosphamide (administration & dosage, adverse effects)
• Doxorubicin (administration & dosage, adverse effects)
• Drug Administration Schedule
• Fatigue (chemically induced)
• Female
• Humans
• Immunoconjugates (administration & dosage, pharmacokinetics, therapeutic use)
• Kaplan-Meier Estimate
• Ki-1 Antigen (metabolism)
• Lymphoma, T-Cell, Peripheral (drug therapy, metabolism)
• Male
• Middle Aged
• Nausea (chemically induced)
• Prednisone (administration & dosage, adverse effects)
• Treatment Outcome
• Vincristine (administration & dosage, adverse effects)
• Vomiting (chemically induced)
• Young Adult