Some early phase II trials in previously untreated multiple myeloma: The Royal Marsden experience

Multiple myeloma is at a stage today where acute leukemia was in the 1960s and 1970s when the aim was to attain complete remission (CR), which would translate into prolonged overall survival (OS) and a cure. The Royal Marsden group was the first to establish a dose-response effect for melphalan leading to CR in patients with myeloma. Since then, different strategies have been developed to improve the results of high-dose therapy, including alternating conditioning regimens, peripheral blood stem cells (PBSC) as a source of stem cells, purging techniques to decrease graft contamination by the myeloma cell, increased dose intensity by means of tandem transplants, and finally, allogeneic matched or unmatched stem cell transplantation. Components of treatment offered at Royal Marsden since 1980 are upfront high-dose melphalan (HDM) 140 mg/m(2), induction infusional chemotherapy followed by consolidation with HDM with autotransplantation, and maintenance with interferon-alpha2b (IFN) (collectively termed sequential therapy). Each of these components has shown benefits in selected studies and together they have dramatically improved the outlook for patients with myeloma.