Trial Information

High -Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma

We have performed over 200 autologous HCT for myeloma at Stanford using high-dose sequential
therapy with a BCNU dose of 550 mg/m2 plus melphalan 200 mg/m2. Analysis of 196 patients
treated this way demonstrates a median event-free survival of 36 months with a median
overall survival of more than six years. The main toxicity of this therapy is related to
BCNU-pneumonitis or interstitial pneumonitis (IP). This complication is related to the dose
of BCNU and is well described in the literature(18). In our myeloma patients treated with
this dose of BCNU the incidence of IP is 34%.

There have been recent studies evaluating the role of tandem autologous transplants for
patients with multiple myeloma. These trials were based upon the hypothesis that performing
tandem high-dose therapy regimens would lead to increased tumor cell kill, decreased tumor
burden and an improvement in overall survival(9, 19). There are trials comparing single to
double transplants that suggest there may be a benefit for tandem autologous transplants for
event-free survival and overall survival (20-22). However, our results with high-dose
sequential therapy including the dose-intense BCNU/Melphalan transplant demonstrates similar
median event-free survival and overall survival when compared with the results of tandem
transplant approaches.

The proposed trial will continue to use a high-dose sequential transplant approach, however,
we will use a reduced dose of BCNU which we expect to be associated with a lower incidence
of IP.