A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma

Abstract

Summary In a phase 2 open‐label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1·0 or 1·3 mg/m2 bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15·7–47·1] and 38% (90% CI, 22·6–56·4) in the 1·0 mg/m2 (8 of 27 patients) and 1·3 mg/m2 (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1·0 and 1·3 mg/m2 cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

“…Although we used 1.0 mg/m 2 of bortezomib in our VRD regimen, the incidence of grade 3/4 peripheral neuropathy was similar with that observed with the dose of 1.3 mg/m 2 of bortezomib in other studies with bortezomib-based regimens 10,37 and higher than that observed with the same dosage of bortezomib-1.0 mg/m 2 in CREST trial (the incidence of peripheral neuropathy was 8%). 37 This may be due to the difference in study population and/or due to the presence of lenalidomide, which can produce severe peripheral neuropathy in 3% of MM patients when it is given as monotherapy 38 and in o1% when it is given in combination with dexamethasone 1 in the relapsed/refractory setting.…”

Bortezomib, Dexamethasone, and High-Dose Melphalan as Conditioning for Stem Cell Transplantation in Young Japanese Multiple Myeloma Patients: A Pilot Study

“…Preclinical evidence provides a rationale for combining bortezomib with dexamethasone, suggesting that the effects of these two agents could be additive and that bortezomib may overcome resistance of MM cell lines to dexamethasone [27]. In two previous trials, bortezomib (1.0 or 1.3 mg/m 2 ) was administered intravenously twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles to patients who had failed second line therapy [10,11,28]. In these trials, patients with progressive disease after two cycles or stable disease after four cycles of bortezomib were eligible for addition of oral dexamethasone (20 mg) on the day of and after each bortezomib dose.…”

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

“…Bortezomib has been demonstrated to be an effective option for MM patients with advanced disease [9][10][11][12][13][14]. However, available published studies included a mixture of patients with multiple and heterogeneous previous regimens.…”

“…In phase 1-2 studies [9][10][11], as well as in community centers compassionate need programs [12,13] bortezomib was effective as single agent in 35-38% (and up to 50%, when dexametasone was added) of patients with advanced MM. 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].…”