High-dose melphalan with autotransplantation for refractory multiple myeloma: Results of a southwest oncology group phase II trial

Purpose: To evaluate high-dose melphalan followed by autologous stem-cell t ransplantation in patients with refractory multiple myeloma. Patients and Methods: Multiple myeloma patients with alkylating agent or vi ncristine/doxorubicin/dexamethasone-refractory disease were eligible for th e phase II multi-institutional Southwest Oncology Group trial $8993, Patien ts up to age 70 years were enrolled between April 15, 1991, and May 1, 1996 . Patients without prior stem-cell collection were primed with high-dose cy clophosphamide (HD-CTX; 6 g/m(2)) and granulocyte-macrophage colony-stimula ting factor. After stem-cell Procurement, patients received melphalan 200 m g/m(2) with autologous transplantation. Upon recovery from melphalan, patie nts were to receive interferon alfa-2b until relapse. Results: Seventy-two Patients were enrolled onto $8993; five were ineligibl e and one received no therapy Of the 66 assessable patients, 56 patients un derwent the transplant procedure; 54 were assessable for response and 56 fo r toxicity. The response to HD-CTX (n = 37) included three complete remissi ons (CRs; 8%) and five partial remissions (PR; 14%); response to melphalan (n = 54) included 16 CRs (30%) and 19 PRs (35%), for an overall CR and grea ter than or equal to PR (n = 66; intent-to-treat) of 27% and 58%, respectiv ely, Toxicities included six treatment-related deaths: two during HD-CTX an d four during transplantation. The median progression-free survival (PFS) a nd overall survival(OS) durations on an intent-to-treat basis from transpla nt registration was 11 months and 19 months (95% confidence interval, 14 to 29 months), respectively. The 3-year actuarial PFS and OS rates were 25% a nd 31%, respectively. Conclusion: High-dose therapy with melphalan 200 mg/m(2) is feasible with h igh response rates (58% overall) and an OS of 19 months in patients with re fractory multiple myeloma. (C) 1999 by American Society of Clinical Oncolog y.