PAD therapy (bortezomib, doxorubicin and dexamethasone) for untreated multiple myeloma (MM)

Abstract

6550 Background: Bortezomib (Velcade, formerly PS341) (P) shows encouraging clinical results in patients (pts) with relapsed MM with dexamethasone showing additive benefit. In vitro, P demonstrates potent synergy with cytotoxics including anthracyclines. Therefore, a Phase I/II study of PAD combination was undertaken in patients with previously untreated MM. The study objectives were: feasibility of peripheral blood stem cell (PBSC) collection and support for high dose melphalan (HDM); safety, toxicity and response rate. Methods: Pts with previously untreated MM were eligible. Pts received 4x21 day cycles of PAD. All pts received P 1.3mg/m2 on days 1,4,8,11 and oral D 40mg days 1–4, 8–11, 15–18 Cycle 1 (day 1–4 only cycles 2–4). Level 1 pts received no doxorubicin [Adriamycin (A)], level 2 pts received 4.5mg/m2 d1–4, level 3 received 9mg/m2 d1–4. Following PBSC harvesting, HDM with PBSC rescue was given. In vitro testing included gene expression analysis on purified plasma cells to identify gene expression profiles associated with response and known prognostic factors. Results: Fifteen pts are enrolled (1F; median age 52 [37–64] yrs) and all have completed at least 1 cycle (Level 1 –3 pts; level 2 –4 pts; level 3 –8 pts). All pts have achieved at least a partial response with 2 achieving a complete response by immunofixation (1 at level 1; 1 at level 3). In 8/8 pts PBSC collection was successful (median 3.13 x106 CD34+ cells/kg (1.92–7.4). 6 pts have completed HDM with PBSCs. Median time to neutrophil (>0.5) and platelet (>20) engraftment was 18 days (13–23) and 12.5 days (10–33). Most adverse events were NCI-CTC Grade 1–2. Of 6 serious adverse events only 2 were considered to be possibly study drug related. There were no deaths on study. Conclusion: PAD is well tolerated, highly effective and does not prejudice PBSC collection or subsequent engraftment. PAD warrants further evaluation in prospective clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc.; Ortho Biotech