S. Vincent Rajkumar, MD

Observation is the standard of care. However, clinical trials are ongoing to determine whether early therapy with newer agents can prolong the time to progression-and most importantly, prolong survival.

Developments in the understanding of multiple myeloma biology have revolutionized our approach to therapy, leading to meaningful improvements in survival.[1] It is becoming increasingly clear that like all tumors, myeloma is a heterogeneous disorder, with different cytogenetic abnormalities, disease kinetics, response to therapy, and prognosis.[2,3] Therefore, a “one size fits all” approach to therapy is no longer tenable for this disease.[4,5] In parallel with this novel understanding of disease biology has been the discovery of novel classes of agents such as the immunomodulatory agents (IMiDs)[6,7] and proteasome inhibitors (eg, bortezomib [Velcade])[8] that alone have significant activity against the disease and more so when used in combination with other agents.

Liposomal doxorubicin received FDA approval for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.

In the past decade there has been arapid increase in our understandingof the biology of multiple myelomaand the development of newtreatment strategies.[1] In the currentissue of ONCOLOGY, Richardson etal provide an excellent overview ofnew agents in the treatment of multiplemyeloma. Two of these agentsare currently available in the UnitedStates outside of clinical trials: thalidomide(Thalomid) and bortezomib(Velcade). The thalidomide analog-lenalidomide (Revlimid)-will likelybe available in the near future,while several other novel agents arebeing evaluated in clinical trials.Richardson and colleagues haveplayed a major role in the developmentof bortezomib and lenalidomide,as well as numerous novel agentscurrently in clinical trials. Their reviewis therefore particularly enlightening,and provides a first-handaccount of the clinical developmentof various new drugs for the treatmentof myeloma.

Standard therapy for multiple myeloma, which accounts for 10% ofall hematologic malignancies, has been autologous stem cell transplantation(ASCT), alkylator-based chemotherapy, and corticosteroids. Severaladvances have been made in the treatment of multiple myelomaover the past decade, especially the arrival of new, active agents suchas thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide(Revlimid). These have shown significant clinical activity as singleagents. Trials are ongoing to incorporate these new agents into thevarious stages of treatment and to combine them with other effectivetreatment modalities, including ASCT.

Over the past decade, remarkable advanceshave been made in the biology and treatmentof multiple myeloma.[1] In most, if not all,patients, myeloma evolves from a precursorstage called monoclonal gammopathy of undeterminedsignificance (MGUS); MGUS isasymptomatic, but progresses to myeloma ora related disorder at a rate of 1% per year.[2]Although precise pathogenetic mechanismsremain elusive, recent studies show that aprimary translocation, usually involvingthe immunoglobulin heavy chain locus onchromosome 14q32, or in some cases theimmunoglobulin lambda light chain locus,can be detected at the MGUS stage in 60-65% of individuals.[3] Progression of MGUSto myeloma appears to be a random eventoften accompanied by secondary translocations(eg, c-myc), mutations in RAS or othergenes, as well as changes in the microenvironmentincluding the induction of angiogenesis.

Tumor angiogenesis is a critical factor in the growth and metastasis of most malignant neoplasms. Thalidomide (Thalomid), banned from clinical use in the 1960s because of severe teratogenicity, has been shown to possess

The use of thalidomide (Thalomid) in the treatment of hematologic diseases and in solid tumors as monotherapy or in combination with other agents is an exciting development in cancer therapy. Researchers actively involved in studying the role of thalidomide in cancer treatment were convened at a special investigators’ meeting held this past May in New Orleans. The articles in this supplement are based on the presentations made at this investigators’ meeting.

Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value in the disease. Based on the increased angiogenesis observed in myeloma, thalidomide (Thalomid) has been studied as