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

TLDR

In this phase‑2 open‑label trial, 54 relapsed or refractory multiple myeloma patients were randomized to receive intravenous bortezomib at 1.0 or 1.3 mg/m² twice weekly for two weeks, then every three weeks up to eight cycles, with optional dexamethasone after two or four cycles, and responses were assessed using modified European Group for Blood and Marrow Transplantation criteria. Bortezomib alone achieved complete or partial responses in 30–38 % of patients, rising to 37–50 % when combined with dexamethasone, with common grade 3 toxicities of thrombocytopenia, neutropenia, lymphopenia, and peripheral neuropathy, and 9 % experiencing grade 4 events, demonstrating therapeutic activity in relapsed or refractory multiple 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/m 2 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/m 2 (8 of 27 patients) and 1·3 mg/m 2 (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/m 2 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.