Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma.
J Clin Oncol. 2006 Sep 25
Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Stadtmauer EA, O'connor OA, Shi H, Boral AL, Goy A.
University of Rochester, James P. Wilmot Cancer Center, Rochester; Weill Medical College of Cornell University/New York Presbyterian Hospital; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Wisconsin, Madison, WI; H. Lee Moffitt Cancer Center, Tampa, FL; Indiana University Medical Center, Indianapolis, IN; University of California Los Angeles School of Medicine, Los Angeles; City of Hope National Medical Center, Duarte, CA; Oregon Health and Science University, Portland, OR; Winship Cancer Institute, Emory University, Atlanta, GA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Millennium Pharmaceuticals Inc, Cambridge, MA; and the Cancer Center at Hackensack University Medical Center, Hackensack, NJ.
PURPOSE: Evaluate response rate, duration of response (DOR), time-to-progression (TTP), overall survival (OS), and safety of bortezomib treatment in patients with relapsed or refractory mantle cell lymphoma (MCL).
PATIENTS AND METHODS: Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 of a 21-day cycle, for up to 17 cycles. Response and progression were determined using International Workshop Response Criteria, both using data from independent radiology review and by the investigators. Primary efficacy analyses were based on data from independent radiology review. RESULTS: In total, 155 patients were treated. Median number of prior therapies was one (range, one to three). Response rate in 141 assessable patients was 33% including 8% complete response (CR)/unconfirmed CR. Median DOR was 9.2 months. Median TTP was 6.2 months. Results by investigator assessments were similar. Median OS has not been reached after a median follow-up of 13.4 months. The safety profile of bortezomib was similar to previous experience in relapsed multiple myeloma. The most common adverse events grade 3 or higher were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). Death from causes that were considered to be treatment related was reported for 3% of patients.
CONCLUSION: These results confirm the activity of bortezomib in relapsed or refractory MCL, with predictable and manageable toxicities. Bortezomib provides significant clinical activity in terms of durable and complete responses, and may therefore represent a new treatment option for this population with usually very poor outcome. Studies of bortezomib-based combinations in MCL are ongoing. |
