Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma

Abstract

SummaryBortezomib, as a single agent and in combination with dexamethasone, was examined as first-line treatment in 32 consecutive patients with untreated symptomatic multiple myeloma. Patients received bortezomib 1AE3 mg/m 2 for a maximum of six 3-week cycles; oral dexamethasone 40 mg was added if a less than partial response (PR) was achieved after two cycles or a less than complete response (CR) was achieved after four cycles. The response rate (CR + PR) was 88%, with undetectable paraprotein (CR) in 6%, and detectable by immunofixation only in 19% [near (n)CR]. All 32 patients completed the first two cycles of bortezomib alone, of whom 3% achieved CR, 9% nCR, and 28% PR. Ten patients received single-agent bortezomib on study, and dexamethasone was added in 22, leading to 15 improved responses. The most common adverse events ‡grade 2 included sensory neuropathy (31%), constipation (28%), myalgia (28%) and fatigue (25%). Sensory neuropathy grade 2 or 3 was reversible within a median of 3 months in five of 10 patients. Bortezomib treatment did not affect stem cell mobilization in eight or transplantation in six patients. Bortezomib alone or in combination with dexamethasone is an effective induction therapy with a high CR and nCR rate and manageable toxicities in previously untreated patients with myeloma.

Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT

“…Similarly, use of bortezomib in the setting of newly diagnosed myeloma has been associated with very high response rates, without compromising the ability to collect stem cells for ASCT. 14 Most recently, use of lenalidomide and dexamethasone has led to high response rates in patients with newly diagnosed myeloma and, especially when combined with lower dose weekly dexamethasone, has been associated with improvement in survival. 15,16 Given the significantly higher response rates associated with the newer regimens, it is not clear that initial therapy with these regimens has any impact on the outcome after transplant.…”

“…[10][11][12][13][14][15][16] Until the introduction of the new drugs, patients eligible for high-dose therapy were usually treated with dexamethasone-based regimens such as VAD or single agent dexamethasone for 4-6 cycles before proceeding to ASCT. Alkylator-based regimens were used rarely in these patients due to concerns that they could impair stem cell collection.…”

“…[6][7][8][9] However, in the past few years several novel, highly effective treatment regimens became available that have been used for initial therapy of the patient with newly diagnosed myeloma. [10][11][12][13][14][15][16] It is not clear if induction therapy with thalidomide or lenalidomide with their higher response rates has any direct impact on the outcome following transplant in patients undergoing ASCT. To address this question, we examined the outcome of patients seen at our institution who underwent ASCT following initial therapy with different regimens.…”

The pathogenesis of the bone disease of multiple myeloma

“…Bortezomib (Velcade™; PS-341) is a potent inhibitor of myeloma cell growth and survival in vitro and results indicate striking therapeutic efficacy and acceptable toxicity profile of intravenous bortezomib in myeloma patients when administered alone or in combination with dexamethasone and/or chemotherapeutic agents, after relapse or at first presentation (70)(71)(72)(73)(74). In addition to myeloma cells, osteoblasts are also sensitive to proteasome inhibitors, and we have recently shown that structurally-unrelated inhibitors of the ubiquitin-proteasome pathway (including bortezomib) have beneficial anabolic effects on the skeleton in vivo (60,75).…”

Bortezomib (Velcade) for progressive myeloma after autologous stem cell transplantation and thalidomide

“…In a recently published phase 3 trial, bortezomib did significantly better than dexamethasone as salvage treatment in MM in terms of response rate, time to progression and survival benefits [14]. Currently, bortezomib, alone or in combination with dexamethasone and doxorubicin, is under investigation as first-line and maintenance therapy, with initial trials demonstrating an overall response rate of about 90%, a substantial proportion of complete or near-complete remissions and the possibility of adequate collections of peripheral blood stem cells [15,16].…”