Abstracts of Annual Education Meeting on 25-Nov-2002
Transplantation in Multiple Myeloma
Catherine Williams, Senior Lecturer and Consultant Haematologist, Christie Hospital, Manchester
Stem cell transplantation for multiple myeloma was first introduced about 15 years ago and remains an important treatment option for many patients. Autologous transplantation has changed over the last 5 years with the move from using bone marrow to peripheral blood as the source of stem cells. As a result, engraftment times are quicker and, with increasingly sophisticated supportive care, the treatment mortality rate has fallen to <3%.
Several randomised trails have now shown it to be superior to conventional chemotherapy alone in terms of complete remission (CR) rates and survival. However, despite this, there is still no plateau seen on the survival curves and autologous transplantation cannot be seen as curative with a median survival in most series of 45-55 months. Measures to try to improve this outcome include maintenance therapy post-transplant, alternative conditioning regimens and tandem transplantation.
Maintenance therapy post-transplant with interferon has only been studied in one randomised trial and this showed no significant difference in EFS or OS. Due to the numerous side-effects profile and poor cost/benefit profile of the drug, many centres have now abandoned its use. Alternative maintenance therapies such as thalidomide and vaccination are under investigation.
Tandem transplantation has been investigated in several randomised studies. The IFM 94 trial showed an increased CR rate and OS, whereas as other series with shorter follow up have not done so. It may take several years of follow up for improved survival following double autografts to show.
Allogeneic transplantation is limited in myeloma to only about 5% of patients due to age and availability of a sibling door. In those who undergo the procedure, about 50% may go into a molecular remission with many of these staying in complete remission for many years. The mortality rate (TRM) of this procedure has always been high, ranging between 30-50% in several series. However, recent data from the EBMT suggests that in the last 5 years the TRM has dropped due to a combination of careful patient selection and improved supportive care. Thus, this approach should be considered for suitable patients under the age of 50 years.
Non-myeloablative transplantation is a relatively new procedure and still very experimental. The aim is to give reduced conditioning, sufficient to allow stem cell engraftment but less toxic than conventional regimens. Series in myeloma patients show the procedure to be relatively safe with a TRM of about 15% but its effect on the disease is still unclear. Various conditioning regimens exist and some have been shown to be useful in relapsed disease, however the more hopeful approach is to use the transplant in tandem with an autologous transplant. Results are encouraging using this approach and a pilot study by the UKMF is currently investigating this.