Breakthroughs in the management of multiple myeloma.

Although multiple myeloma remains a terminal illness, the past four decades have seen a dramatic change in the outlook for a newly diagnosed patient in terms of therapies available, supportive care and insight into the pathogenesis of this disease. Among the newer agents available for treatment, thalidomide has been resurrected and discovered to be a valuable therapy for myeloma. Thalidomide appears to work, at least in part, through its anti-angiogenic properties, but much remains to be learned about its mechanism of action as well as optimal administration regimens. With the development of increasingly more potent bisphosphonates it has become possible to diminish the painful skeletal complications of myeloma, one of the most devastating problems of this disease. The most recent generation of bisphosphonates, pamidronic acid and zoledronic acid, have provided a statistically significant decrease in the skeletal complications of myeloma when used in a prophylactic manner. These agents appear to work by inhibiting osteoclast function. Progressive improvement in cytogenetic techniques has now demonstrated that almost all patients with myeloma have chromosomal abnormalities, some of which appear to confer varying degrees of prognostic significance. In particular, the changes in chromosome 13 are associated with an unusually poor outcome. These findings are serving as a guide toward learning more about the pathogenesis of myeloma as well as in identifying potential targets for therapy. Stem cell transplantation has emerged as the standard treatment for the large majority of patients with myeloma following the demonstration of superior complete remission and survival, both disease-free and overall, in a French randomised trial. Unfortunately, virtually all patients will eventually relapse following autologous stem cell transplantation, prompting continuing efforts such as tandem transplants, CD34+ selection, as well as modifications in the conditioning regimen to improve outcomes. Allogeneic bone marrow transplants appear to offer a better chance for a possible cure of myeloma but have been associated with an unusually high mortality. However, this approach is being revived with the advent of the less toxic non-myeloablative transplant that has provided an 81% short-term survival in a trial combining this approach with an initial conventional autologous bone marrow transplant. Immunotherapy with dendritic cells appears now to be a feasible way to enhance innate or acquired immunity to help eliminate minimal residual disease following autologous bone marrow transplant. Unfortunately, a cure for myeloma remains elusive but the continuing advances in management may significantly prolong survival in affected patients.