FDA Approves Velcade for Relapsed Mantle-Cell Lymphoma

ROCKVILLE, Maryland-The FDA has granted approval to Velcade (bortezomib for injection, Millennium) for the treatment of mantle cell lymphoma (MCL) in patients who have received at least one prior treatment. Velcade is the first agent approved for use in relapsed or refractory MCL patients, for whom no standard of care has existed. Velcade is a proteasome inhibitor, which Millennium co-developed with Johnson & Johnson.

Velcade was initially approved in May 2003 for use in treating multiple myeloma in patients who have received at least one prior treatment. The drug is currently in clinical trials in newly diagnosed multiple myeloma patients and in other types of non-Hodgkin's lymphoma, including an international phase III trial of Velcade plus rituximab (Rituxan).

To support its supplemental indication in MCL, Millennium submitted data from the prospective PINNACLE trial, an open-label, single-arm, multicenter study of 155 patients with progressive MCL who had undergone at least one prior therapy.

Among the participants, 75% had one or more extranodal disease sites; 77% had stage IV disease; 91% had prior therapy that included an anthracycline or mitoxantrone, cyclophosphamide, and rituximab; and 37% were refractory to their last therapy. Patients received 1.3 mg/m² of Velcade intravenously on days 1, 4, 8, and 11 of each 3-week cycle.

The PINNACLE results showed an overall response rate of 31% (median duration, 9.3 months); a complete response rate (CR + unconfirmed CR) of 8% (median duration, 15.4 months); a median time to response of 40 days (range, 31 to 204 days); and a median time to progression of 6.2 months.

Adverse events were similar to those seen in previous myeloma studies. The leading treatment-emergent problems were asthenic conditions (72%), peripheral neuropathies (55%), constipation (50%), diarrhea (47%), nausea (44%), and decreased appetite (39%). Peripheral neuropathy was the most common event leading to discontinuation.