Multiple myeloma represents c. 10-15% of all haematological malignancies (blood and bone marrow cancers). According to the Australian Institute of Health and Welfare in 2015 1,891 people were diagnosed with Multiple Myeloma, with 905 deaths in 2016.
Each year in Australia around 1,800 people are diagnosed with multiple myeloma. Although treatment advances have progressed improving survival outcomes, most patients eventually relapse and develop resistance to their treatments. Depending on prognostic factors, multiple myeloma has a median survival rate of 4-7 years, with a five-year relative survival rate at around 50% and with a 10-year survival rate of approximately 27%.
Multiple myeloma is an incurable B-cell malignancy characterised by the aberrant expansion of clonal malignant plasma cells into bone marrow that eventually causes renal failure, anemia, infection and/or osteolytic bone lesions, clinically categorised as CRAB – Hyper Calcaemia, Renal failure, Anaemia and/or Bone lesions. The cancerous cells are called myeloma cells. It is one of the three most common blood cancers.
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Multiple causes of multiple myeloma have been suggested such as exposure to certain industrial and environmental chemicals, radiation and viruses, although none have been proven. It is not considered hereditary though family connections have been noted.
When plasma cells become cancerous and grow out of control, they can produce a tumour called a plasmacytoma. These tumours generally develop in a bone, but they are also rarely found in other tissues. If someone has only a single plasma cell tumour, the disease is called an isolated (or solitary) plasmacytoma. If someone has more than one plasmacytoma, they have multiple myeloma.
As only a very small percentage of young adults are diagnosed with multiple myeloma, with the majority of those diagnosed being over 60 years old, a material number of patients are either ineligible or unwilling to undergo high dose melphalan and (allogenic or autologous) stem cell transplantation (HDM/SCT). HDM/SCT is an aggressive form of therapy that has been shown to prolong progression-free and overall survival. In multiple myeloma, the efficacy of immunotherapy is based on the observation that allogenic stem cell transplantation is curative for a subset of patients due to the graft-versus-myeloma effect, however for those patients who are not eligible for HDM/SCT reliance must be placed on other anti-plasma cell approaches, which include:
With the advent of iMiDs, proteasome inhibitors and mAbs, deep responses have become more readily achievable and with the use of multidrug combinations that incorporate iMiDs and/or proteasome inhibitors, the response rate that can now be achieved is comparable with that achieved with HDM-SCT in the 1990s and early 2000s.
