Elsevier

The Lancet

Volume 385, Issue 9983, 30 May–5 June 2015, Pages 2197-2208
The Lancet

Seminar
Multiple myeloma

https://doi.org/10.1016/S0140-6736(14)60493-1Get rights and content

Summary

Multiple myeloma is a malignant disease characterised by proliferation of clonal plasma cells in the bone marrow and typically accompanied by the secretion of monoclonal immunoglobulins that are detectable in the serum or urine. Increased understanding of the microenvironmental interactions between malignant plasma cells and the bone marrow niche, and their role in disease progression and acquisition of therapy resistance, has helped the development of novel therapeutic drugs for use in combination with cytostatic therapy. Together with autologous stem cell transplantation and advances in supportive care, the use of novel drugs such as proteasome inhibitors and immunomodulatory drugs has increased response rates and survival substantially in the past several years. Present clinical research focuses on the balance between treatment efficacy and quality of life, the optimum sequencing of treatment options, the question of long-term remission and potential cure by multimodal treatment, the pre-emptive treatment of high-risk smouldering myeloma, and the role of maintenance. Upcoming results of ongoing clinical trials, together with a pipeline of promising new treatments, raise the hope for continuous improvements in the prognosis of patients with myeloma in the future.

Section snippets

Epidemiology

Multiple myeloma is the malignant counterpart of long-lived plasma cells with a strong tropism for bone and bone marrow. Among other plasma cell dyscrasias, such as Waldenström's macroglobulinaemia and primary amyloidosis, multiple myeloma is the second most frequent haematological malignancy with an age-adjusted incidence of six per 100 000 per year in the USA and Europe. The incidence of multiple myeloma is two to three times higher in African Americans, making it the most common

Pathogenesis

Multiple myeloma cells are similar to long-lived, post-germinal centre plasma cells, and are characterised by strong bone marrow dependence, extensive somatic hypermutation of immunoglobulin genes, and absence of IgM expression. However, multiple myeloma cells differ from healthy plasma cells because they retain the potential to return to a lower proliferative state.3

Symptoms, diagnostic workup, and disease monitoring

The most common clinical manifestations of symptomatic multiple myeloma are anaemia, infections, lytic or osteopenic bone disease, or renal failure, but patients with multiple myeloma might be diagnosed at an asymptomatic stage by chance. Generally, multiple myeloma is diagnosed at an earlier stage today than in the past.8 Back pain, particularly in older patients, or unclear anaemia should prompt screening for the presence of multiple myeloma. The standard screening workup includes total serum

Indication for treatment

Patients with smouldering multiple myeloma have no treatment indication and should be monitored for disease progression because early treatment with conventional therapy has shown no benefit.17, 18, 19 The risk of progression is highest in the first 5 years and decreases subsequently. The overall risk of progression is 10% per year for the first 5 years, about 3% per year for the next 5 years, and 1% per year for the next 10 years.17 Patients with high-risk smouldering multiple myeloma should

Future perspectives

The growing knowledge about pathogenic mechanisms, the development of novel effective compounds that target both multiple myeloma cells and the microenvironment, and more effective supportive strategies have led to a prolonged median overall survival of patients with multiple myeloma over the past two decades.107 As shown in a single treatment centre, 5-year overall survival improved from 37% in patients treated between 1971 and 1996, to 52% between 1997 and 2006 (figure 4), and 66% between

Search strategy and selection criteria

Data for this Seminar were identified by searches of PubMed, Embase, Web of Science, and Cochrane Library for reports published between Nov 1, 2008, and March 31, 2013, online accessible abstract collections from 2012 annual meetings of the American Society of Haematology, American Society of Clinical Oncology, and European Society of Haematology. Search terms used were “myeloma”, “pathogenesis”, “diagnosis”, “treatment”, and “therapy”; MeSH terms and filters for randomised trials were used if

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