Bortezomib for the treatment of mantle cell lymphoma.
OBJECTIVE
To describe the Food and Drug Administration review and marketing approval considerations for bortezomib (Velcade) for the treatment of patients with mantle cell lymphoma.


METHODS
Food and Drug Administration reviewed a multicenter study of bortezomib in 155 patients with progressive mantle cell lymphoma after at least one prior therapy.


RESULTS
Seventy-seven percent were stage IV, and 75% had one or more extranodal sites of disease. Prior therapy included an anthracycline or mitoxantrone, cyclophosphamide, and rituximab. Median age was 65 years. All received bortezomib 1.3 mg/m(2) i.v. on days 1, 4, 8, and 11 of each 3-week cycle. The primary end point was response. Response and progression were determined by independent review of serial computed tomography scans using International Lymphoma Workshop Response Criteria. The overall response rate was 31%, including complete response (CR) plus CR unconfirmed (CRu) plus partial response; median response duration was 9.3 months. The CR plus CRu response rate was 8% with a median duration of 15.4 months. Adverse events were similar to those observed previously for bortezomib. The most commonly reported treatment-emergent adverse events were asthenia (72%), peripheral neuropathies (55%), constipation (50%), diarrhea (47%), nausea (44%), and anorexia (39%). The most common adverse event leading to discontinuation was neuropathy.


CONCLUSIONS
Bortezomib received regular approval for the treatment of patients with mantle cell lymphoma in relapse after prior therapy.
Kane
Robert C
RC
Division of Drug Oncology Products, Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA. robert.kane@fda.hhs.gov
Dagher
Ramzi
R
Farrell
Ann
A
Ko
Chia-Wen
CW
Sridhara
Rajeshwari
R
Justice
Robert
R
Pazdur
Richard
R
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D017277:Drug Approval; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib