Related Pages Multiple Myeloma/Other Plasma Cell Neoplasms NCI's gateway for information about multiple myeloma and other plasma cell neoplasms. Drug Information Summaries NCI's drug information summaries provide consumer-friendly information about certain drugs that are approved by the U.S. Food and Drug Administration (FDA) to treat cancer or conditions related to cancer.

Brand name(s): Velcade®

• Approved for multiple myeloma (two prior therapies), May 13, 2003
• Approved for multiple myeloma (one prior therapy), March 25, 2005
• Approved for mantle cell lymphoma (one prior therapy), Dec. 8, 2006

Multiple Myeloma (two prior therapies)

On May 13, 2003, under accelerated approval provisions, the U.S. Food and Drug Administration (FDA) approved bortezomib (Velcade®, a trademark of Millennium Pharmaceuticals, Inc.) for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy.

Bortezomib was evaluated in 256 patients with multiple myeloma in two open-label multicenter studies conducted in the United States. In the primary efficacy study, 202 patients were entered after having received at least two prior therapies and progressing on the most recent therapy. Bortezomib was administered intravenously at 1.3 milligrams (mg) /m2/dose twice weekly for two weeks, followed by a 10-day rest period (21 day treatment cycle) for a maximum of eight treatment cycles. In the study population, the median number of prior therapies was six, and 64 percent of patients had received stem cell transplant or other high dose therapy. Results (Blade criteria) in the 188 eligible and evaluable patients included complete responses in five patients, for a complete response rate of 2.7 percent (95 CI: 1 percent, 6 percent); partial responses occurred in 47 patients for a PR rate of 25 percent (95 CI: 19 percent, 32 percent). Clinical remissions by SWOG criteria were observed in 17.6 percent of patients (95CI: 12 percent, 24 percent). Median duration of response was 365 days.

Adverse events (AEs) occurring in greater than 50 percent of patients included fatigue or malaise, nausea, and diarrhea. AEs occurring in greater than 30 percent of patients were anorexia, constipation, thrombocytopenia, peripheral neuropathy, pyrexia, vomiting, and anemia. Severe AEs with incidences greater than 10 percent were thrombocytopenia, peripheral neuropathy, neutropenia and asthenia.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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Multiple Myeloma (one prior therapy)

On March 25, 2005, the FDA approved bortezomib for the treatment of patients with multiple myeloma who have received at least one prior therapy.

The May 13, 2003, accelerated approval was based on response rate and response durability. The post-marketing commitments have been fulfilled with the results of the trial described below.

Safety and efficacy were demonstrated in one multicenter, controlled clinical trial of 669 myeloma patients who had received at least one prior therapy. These patients were randomized to receive either bortezomib, 1.3 mg/m2 intravenous bolus on days 1, 4, 8, 11 of each three week cycle for eight weeks or dexamethasone, 40 mg/day by mouth once daily on Days 1 to 4, 9 to 12, and 17 to 20 every five weeks for four cycles. Each arm also had a reduced-dose schedule for further treatment cycles. The primary endpoint was time-to-progression (TTP). Following a planned interim analysis, the study was terminated early on the advice of a Data Monitoring Committee.

Bortezomib demonstrated a statistically significant improvement in TTP (HR=0.55, [0.44, 0.69], p <0.0001) and response rate (38 percent versus 18 percent; p < 0.0001). Overall survival was prolonged for patients on the bortezomib arm (HR=0.57, p value < 0.05) compared to the dexamethasone arm.

Adverse events were similar to those previously reported for bortezomib. Among the 331 patients treated with bortezomib, the most commonly reported adverse events were asthenic conditions, diarrhea, nausea, fatigue, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, anemia, headache, anorexia, cough, and paresthesia. Other adverse events included dyspnea, neutropenia, rash, insomnia, and bone pain. Myelosuppression was moderate in degree and reversible. Neuropathy was slowly reversible. Heart failure and possible tumor lysis syndrome were added to the label warnings in mid-2004.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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Mantle Cell Lymphoma (one prior therapy)

On December 8, 2006, the FDA granted approval to bortezomib for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy.

An open-label, single-arm, multi-center study of 155 patients with progressive mantle cell lymphoma who had received at least one prior therapy was performed to assess response rate and duration. Seventy-five percent had one or more extra-nodal disease sites and 77 percent were stage 4.

In 91 percent of patients, prior therapy included an anthracycline or mitoxantrone, cyclophosphamide, and rituximab. Thirty-seven percent were refractory to their last prior therapy. Patients received bortezomib,1.3 mg/m2 intravenously, on days 1, 4, 8, and 11 of each three week cycle.

Response rates were determined according to the International Workshop Response Criteria (1999) and were based on an independent radiologic CT scan review. The overall response rate (CR plus CRu plus PR) was 31 percent and the median response duration was 9.3 months. The CR plus CRu response rate was 8 percent and the median response duration was 15.4 months. The median number of cycles in responding patients was eight. The median time to response was 40 days (range 31 to 204 days).

Adverse events, irrespective of their relationship to bortezomib, were similar to those observed in the previously reported myeloma studies (see product labeling). The most commonly reported treatment-emergent adverse events were asthenic conditions (72 percent), peripheral neuropathies (55 percent), constipation (50 percent), diarrhea (47 percent), nausea (44 percent), and appetite decreased (39 percent). The most common adverse event leading to discontinuation was peripheral neuropathy. For safe use of bortezomib, patients must be kept well hydrated.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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