Updated Survival Analyses after Prolonged Follow-Up of the Phase 2, Multicenter CREST Study of Bortezomib in Relapsed or Refractory Multiple Myeloma.

Background: The initial report of the CREST phase 2 study (Br J Haematol2004;127:165–72) demonstrated the substantial activity of bortezomib (VELCADE®, Vc) at two different dose levels in patients with relapsed or refractory multiple myeloma (MM). Here, we provide an updated analysis of overall survival (OS) after prolonged follow-up (median >5 years). Methods: 54 patients were enrolled to receive Vc 1.0 mg/m 2 (n=28) or 1.3 mg/m 2 (n=26) on days 1, 4, 8, and 11 of a 21-day cycle, for up to 8 cycles. Dexamethasone (dex) 20 mg on the day of and day after each Vc dose was added for 16 (57%) patients in the 1.0 mg/m 2 group and 12 (46%) patients in the 1.3 mg/m 2 group, upon suboptimal response to Vc alone. A total of 17 (31%) patients continued to receive Vc ± dex in an extension study, 12 (43%) from the 1.0 mg/m 2 and 5 (19%) from the 1.3 mg/m 2 groups. Patients received a median of 3 (range, 1–7) prior regimens. Median time from diagnosis to first Vc dose was 2 years. In the 1.0 and 1.3 mg/m 2 groups, respectively, mean age was 64 vs 60 years, 50% vs 35% of patients were male, 54% vs 65% had IgG MM, 58% vs 48% had β 2 -microglobulin ≥4 mg/L, and 29% vs 48% had abnormal cytogenetics. Response rate (CR+PR, EBMT criteria) to Vc alone was 30% vs 38%, and to Vc ± dex was 37% vs 50% in the 1.0 and 1.3 mg/m 2 groups. OS from first dose of Vc in each dose group was analyzed using the Kaplan-Meier method. Results: Median OS in the 1.0 and 1.3 mg/m 2 groups was 26.8 months and 60.0 months, after median follow-up of 61 and 65 months, respectively (Figure). In the 1.0 mg/m 2 group, 21 (75%) patients have died; the 1- and 2-year OS rates were 82% and 54%, respectively. In the 1.3 mg/m 2 group, only 14/26 (54%) patients have died; 1- and 2-year OS rates were 81% and 69%, respectively. Conclusions: Vc ± dex was active in relapsed or refractory MM at both the 1.0 mg/m 2 and 1.3 mg/m 2 dose levels and was associated with notable OS, particularly in patients treated with the approved Vc dose of 1.3 mg/m 2 . The difference in OS between dose groups suggests that the higher dose of Vc is more active. Figure. Kaplan-Meier analyses of OS in patients who received Vc 1.0 mg/m 2 (n=28) or 1.3 mg/m 2 (n=26).