Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma

Randomized trials conducted by the Intergroupe Francaise du Myelome (IFM) d emonstrate that the use of high-dose chemotherapy (HDCT) and stem cell tran splantation (SCT) improves event-free (EFS) and overall survival (OS) in yo unger patients with multiple myeloma (MM). Nevertheless, current HDCT regim ens remain inadequate as all patients ultimately relapse following SCT, In an attempt to improve the OS of MM patients post-SCT we used an escalated H DCT regimen incorporating both intensified melphalan (160 mg/m(2)) and frac tionated total body irradiation (12 Gy) to maximize the dose response of my eloma cells to these agents and included infusional etoposide 60 mg/kg in a n attempt to eradicate clonal B cells potentially contributing to the myelo ma clone. One hundred patients with MM received this intensified SCT regime n. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of who m 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transp lant is 41 months and the median EFS is 28 months. More than two prior chem otherapy regimens, previous radiation therapy (RT) and the presence of an a bnormal karyotype involving chromosomes 11 or 13 were significantly predict ive of poor outcome. Interferon maintenance was not associated with improve d outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.