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Background: High-dose melphalan followed by autologous stem cell rescue has been shown to significantly increase progression free survival and overall survival in patients with multiple myeloma. Renal failure (RF) often precludes patient enrollment in studies involving high dose mephalan conditioning for autologous stem cell transplant (ASCT) due to increased treatment-related morbidity and mortality. However, several studies have shown that RF should not be an exclusion criterion and early ASCT could be helpful in treating patients with MM and RF, but the preferred conditioning regimen has yet to be determined as data is limited. Also, most of these studies have used a one-day washout for melphalan prior to stem cell infusion.
Patients and methods: We conducted a retrospective study of 17 patients with multiple myeloma on hemodialysis who underwent ASCT over a period of 8 years at a single institution. All patients underwent ASCT with the same conditioning regimen that consisted of melphalan 70mg/m2 days -4 and -3, for a total of melphalan 140mg/m2, followed by a two-day washout period on days -2 and day -1 with stem cell infusion on day 0. Patients underwent hemodialysis on day -4 prior to the first dose of melphalan, day -2 (24 hours after 2nd dose of melphalan is given), and again on day 0. A two-day washout was used to allow a longer duration for melphalan to clear prior to stem cell infusion. OS was calculated from day of transplant to date of death or last follow up.
Results: A total of 17 patients on hemodialysis with multiple myeloma underwent ASCT between April 2006 and May 2014 with high-dose melphalan and two day washout. The median number of therapies prior to transplant was 1.5 (range, 1-3) with only 4 (24%) of patients ≥VGPR at the time of transplant. There were 6 (35%) patients with grade III toxicity (majority were mucositis) and no grade IV toxicities reported. The median time to engraftment was 11 days (range, 10-16) and the best response post-ASCT by 1year evaluation included the following: 11 (65%) patients with CR, 2 (7%) VGPR, 3 PR (18%), 1 (6%) patient with stable disease, and 1 patient was inevaluable because of death before 1 year post-ASCT response assessment. There were no deaths within the 100 days of ASCT however one patient died of septic shock before 1 year post-ASCT response assessment. At a median follow up of 2.7 years, the overall survival was ~6.5 years (Figure 1).
Conclusions: This is a single institution retrospective study demonstrating that high dose melphalan with a two day washout in patients with multiple myeloma on hemodialysis is a safe regimen with a lower toxicity, reduced mortality and deep remissions. Future prospective studies are needed to confirm the reduced toxicity and continued benefit of this approach.
Figure 2 Time to progression
