Update of melphalan 280 mg/m2 plus amifostine cytoprotection before autologous stem cell transplantation as part of initial therapy in multiple myeloma patients

Abstract

7608 Background: Autologous stem cell transplantation (ASCT) using melphalan 200 mg/m2 is a standard part of inital therapy in younger multiple myeloma (MM) patients (pts). We have previously reported an augmented regimen of melphalan 280 mg/m2 with the cytoprotectant agent amifostine (AF) to try to improve the anti-tumor response without increased mucosal toxicity (The Hematol J 2003; 4[suppl]: S207). We now update our experience with this regimen. Methods: Pts without disease progression and adequate organ function (creatinine clearance at least 60 cc/min) were eligible. Pts were treated as part of phase I-II trials approved by each center’s institutional review board. AF 740 mg/m2 was given IV over 5–15 min 24 hr and 15 min prior to melphalan 280 mg/m2 (infused over 15 min). Blood stem cells were reinfused 24 hrs later. The primary endpoint was response rate at day 100. Regimen-related toxicity using the Seattle criteria, progression-free (PFS) and overall survival (OS) were also assessed. Results: 24 pts were transplanted between 5/99–7/02. Median age was 50 (32–65) yrs; 1 pt had primary amyloidosis; median beta2-microglobulin level at diagnosis was 1.98 (0.88–11.80) mg/L. Prior therapy included VAD in 14, dexamethasone alone in 7 plus other regimens in 7. Day 100 responses compared with with pre-ASCT values included CR in 11, near CR (immunofixation positivity only) in 1, VGPR (greater than 90% reduction in serum M protein) in 3, PR in 5 and stable disease in 3. Maximum grade of mucositis was 2 (5 pts); no grade 3 or 4 toxicity was seen. The median day of ANC recovery to 0.5 x 109/L and median day of last platelet transfusion were 11 (6–16) and 10 (7–32), respectively. 4 received thalidomide (1 briefly), while 1 was treated with maintenance alpha interferon after day 100. Median follow-up is 52 (9–72) mos. 7 pts are alive without progression, including 5 in CR and 2 in PR. 16 have progressed at a median of 15 (7–36) mos post-ASCT. 8 have died from MM (7) or lung cancer (1). The 4 yr actuarial PFS is 28% (95% C.I. 34–76%) and OS 58% (95% C.I.11–47%). Conclusions: 1) Melphalan 280 mg/m2 with AF is well-tolerated; 2) the CR + nCR + VGPR rate of 62% warrants further evaluation, perhaps as part of tandem transplants or in conjuction with novel agents. [Table: see text]