European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Although multiple myeloma (MM) is incurable with currently available treatments, the introduction of thalidomide and the development of safer and more active thalidomide analogues represent a major advance in the therapy of this disease. Thalidomide, initially introduced for treatment of MM because of its anti-angiogenic properties, has shown remarkable activity alone and in combination with other drugs in patients across all stages of the disease. Given the potential for teratogenicity with thalidomide and the non-haematologic toxicities of the drug, several analogues referred to as "immunomodulatory drugs" (IMiDs) were developed with the intent of enhancing the immunomodulatory effect while minimizing the teratogenic risk. ⋯ Lenalidomide has shown impressive activity in relapsed refractory myeloma as well as newly diagnosed disease. The precise mechanism of anti-MM activity of thalidomide and the IMiDs is not clear, but studies suggest that several other mechanisms besides anti-angiogenic effects may play a role. In this paper we review the development, pharmacology, mechanism of action, pre-clinical and clinical efficacy, and the current status of thalidomide and the IMiDs in the treatment of MM.
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Treatment for multiple myeloma (MM) has changed beyond recognition in the past decades. While until the early 1980s, MM caused a slow progressive decline in quality of life until death after about two years, today's patients can expect a 50% chance of achieving a complete remission, a median survival time of five years and a 20% chance of surviving longer than ten years. State of the art therapy comprises: evidence-based supportive care; highly effective and well tolerated chemotherapeutic regimens; and for patients qualifying for intensive high-dose conditioning, autologous haematopoietic stem cell transplantation (HSCT) is an option. ⋯ In addition, improved understanding of the disease biology has led to the development of novel biological treatment agents, such as thalidomide, bortezomib and others, targeted at cellular mechanisms and interactions, e.g. with the bone marrow microenvironment. These strategies are incrementally integrated into modern MM care. This review considers recent clinical advancements in anti-myeloma strategies and provides an overview of the state of the art management of MM patients.
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Based on Medline search, a summary is provided of recent health economic evidence in published literature relating to the management of multiple myeloma. The following major components of current multiple myeloma treatments are discussed: induction chemotherapy, high-dose chemotherapy supported by autologous peripheral stem cell transplantation (ASCT), long-term biphosphonates therapy to prevent skeletal events and recent advances for the treatment of relapsed or refractory multiple myeloma and under evaluation in primary treatment (thalidomide and bortezomib). Our study shows that there still appears to be a need for health economic information to confirm the cost-effectiveness of stem cell support versus high-dose chemotherapy without stem cell support, as well as to assess optimal biphosphonate treatment regimens. There is also a clear need for peer reviewed economic evaluations of novel therapies such as thalidomide and Bortezomib in the treatment of multiple myeloma at different stages of the disease.