Inclusion of High-Dose Treosulfan Followed by Autologous Transplantation in the Tandem Transplantation for Patients with Multiple Myeloma <60 Years.

High-dose treosulfan followed by autologous transplantation is a tolerable and efficacious regimen in quite different tumor types. Aim of the present study was to proof safety and efficacy of high-dose treosulfan in an intraindividual comparison with melphalan. Between August 2003 and July 2006, 20 patients with multiple myeloma, age< 60 years were enrolled onto an unicentric phase II trial. The median age was 55 years. All patients received pretreatment with 3 to 4 cycles idarubicin and dexamethasone (90%) or CAD (10%). After induction the peripheral blood stem cells were mobilized with a combination of ifosfamide, epirubicin, etoposide (IEV) followed by G-CSF. Stem cell harvest was successful in all patients. Thereafter, the patients received tandem transplantation in an interval of 2 months, first after conditioning with high-dose treosulfan on day −4 to −2, 14g/m2 daily, then after high-dose melphalan 140 mg/m2. Maintenance therapy with interferon-alpha was administered in 30% of the cases. For all patients the completion rate of the first transplantation was 100%, for the second 85%. Three patients did not proceed to the second autologous transplantation due to a severe ischemic colitis (n= 1) or a high-risk profile (allogeneic transplantation in 2 cases). Two patients received an allogeneic transplantation during the further course of the disease. Overall the conditioning regimens were well tolerable. Hematotoxicity grade 4 was observed after each high-dose cycle. Grade 3/4 infections and stomatitis were present in 5%/5% after treosulfan and in 18%/6% after melphalan. An acute coronary heart syndrome occurred after Mel140. The duration of severe leukopenia (< 1.0 leukocytes) was significantly shorter after treosulfan (6.4 days vs. 7.9 days, p= 0.009), whereas time to leukocyte recovery did not significantly differ between the regimens. No treatment related deaths occurred. Best response after transplantation was CR 30%, PR 60%, NC 5%, and PD 5%. In comparison to the preceding chemotherapy a further >50% decline of the paraprotein was achieved by treosulfan in 3 cases, by melphalan in 2 cases. In the intraindividual comparison treosulfan and melphalan, respectively, have shown two times superior response. The median event-free survival was 28 months, and the overall survival at 4 years was 81%. In conclusion, high-dose treosulfan may be more favorable for patients at risk for infections than melphalan, and seems to be as efficacious as melphalan for the treatment of multiple myeloma. Treosulfan should be further investigated in multiple myeloma patients.