Originally published as JCO Early Release 10.1200/JCO.2006.07.9665 on September 25 2006

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fisher, R. I. Articles by Goy, A. Search for Related Content PubMed PubMed Citation Articles by Fisher, R. I. Articles by Goy, A.

Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Richard I. Fisher, Steven H. Bernstein, Brad S. Kahl, Benjamin Djulbegovic, Michael J. Robertson, Sven de Vos, Elliot Epner, Amrita Krishnan, John P. Leonard, Sagar Lonial, Edward A. Stadtmauer, Owen A. O'Connor, Hongliang Shi, Anthony L. Boral, André Goy

From the 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

Address reprint requests to Richard I. Fisher, MD, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642; e-mail: Richard_Fisher{at}urmc.rochester.edu

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/m² 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.

published online ahead of print at www.jco.org on September 25, 2006.

Supported by Millennium Pharmaceuticals Inc and Johnson & Johnson Pharmaceutical Research & Development LLC.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005 and the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

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

This article has been cited by other articles:

				R. W. Chen, L. T. Bemis, C. M. Amato, H. Myint, H. Tran, D. K. Birks, S. G. Eckhardt, and W. A. Robinson Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma Blood, August 1, 2008; 112(3): 822 - 829. [Abstract] [Full Text] [PDF]

				K. N. Utecht and J. Kolesar Bortezomib: A novel chemotherapeutic agent for hematologic malignancies Am. J. Health Syst. Pharm., July 1, 2008; 65(13): 1221 - 1231. [Abstract] [Full Text] [PDF]

				J. H. Mendler, J. Kelly, S. Voci, D. Marquis, L. Rich, R. M. Rossi, S. H. Bernstein, C. T. Jordan, J. Liesveld, R. I. Fisher, et al. Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma Ann. Onc., May 25, 2008; (2008) mdn365v1. [Abstract] [Full Text] [PDF]

				S. Michopoulos, K. Petraki, C. Matsouka, E. Kastritis, H. Chrysanthopoulou, and M. A. Dimopoulos Mantle-Cell Lymphoma (Multiple Lymphomatous Polyposis) of the Entire GI Tract J. Clin. Oncol., March 20, 2008; 26(9): 1555 - 1557. [Full Text] [PDF]

				R. Z. Orlowski and D. J. Kuhn Proteasome Inhibitors in Cancer Therapy: Lessons from the First Decade Clin. Cancer Res., March 15, 2008; 14(6): 1649 - 1657. [Abstract] [Full Text] [PDF]

				R. Piva, B. Ruggeri, M. Williams, G. Costa, I. Tamagno, D. Ferrero, V. Giai, M. Coscia, S. Peola, M. Massaia, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib Blood, March 1, 2008; 111(5): 2765 - 2775. [Abstract] [Full Text] [PDF]

				B. S. Kahl New Therapeutic Strategies for Mantle Cell Lymphoma ASCO Educational Book, January 1, 2008; 2008(1): 392 - 397. [Abstract] [Full Text] [PDF]

				G. Cavaletti and E. Nobile-Orazio Bortezomib-induced peripheral neurotoxicity: still far from a painless gain Haematologica, October 1, 2007; 92(10): 1308 - 1310. [Full Text] [PDF]

				M. Wang, L. Zhang, X. Han, J. Yang, J. Qian, S. Hong, F. Samaniego, J. Romaguera, and Q. Yi Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways Blood, June 15, 2007; 109(12): 5455 - 5462. [Abstract] [Full Text] [PDF]

				S. P. Treon, Z. R. Hunter, J. Matous, R. M. Joyce, B. Mannion, R. Advani, D. Cook, J. Songer, J. Hill, B. R. Kaden, et al. Multicenter Clinical Trial of Bortezomib in Relapsed/Refractory Waldenstrom's Macroglobulinemia: Results of WMCTG Trial 03-248 Clin. Cancer Res., June 1, 2007; 13(11): 3320 - 3325. [Abstract] [Full Text] [PDF]

				P. Perez-Galan, G. Roue, N. Villamor, E. Campo, and D. Colomer The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak Blood, May 15, 2007; 109(10): 4441 - 4449. [Abstract] [Full Text] [PDF]