Multiple Myeloma

Summary
Multiple Myeloma (MM) is a series of hematological malignant disease, in which there is abnormal proliferation of neoplastic plasma cells that secrete large amounts of monoclonal immunoglobulin (M protein), resulting in extensive bone destruction, and repeated infection, anemia, hypercalcemia, hyper viscous syndrome and renal insufficiency. There is high incidence in the middle-aged and elderly people. The overall incidence of MM is 1.5-2/100000, ranking second in hematological malignancies.
Causes
The cause of multiple myeloma remains is unclear, possibly due to genetic factors, ionizing radiation, chronic antigen stimulation, genetic factors, virus infection, which may be related to the occurrence of the disease.
Symptions
Often in Multiple myeloma patients with asymptomatic in the early stage, or only erythrocyte sedimentation rate increased, anemia and proteinuria et al. The lack of specific symptoms, Early diagnosis of MM is very difficult. then easy to misdiagnose.
 
Typical clinical manifestations of MM are hypercalcemia, renal insufficiency, anemia and bone disease, which namely “CRAB”. Normal immunoglobulin production suppressed cause infections in MM.
 
Bone disease - About 75% of patient with multiple myeloma may occurs bone pain. in which back pain is the most common, with progressively increasing pain. It mainly involves flat bone, irregular bone and long bone. which the main X-ray findings osteolytic defect and systemic osteoporosis;
The slight exertion or injury can lead to fracture, which are most vulnerable to fracture-the spine and ribs.
 
Hypercalcemia - The destruction of bone leads to the loss of calcium to blood .so it causes hypercalcemia, which occurs in about 30-40% of patients with multiple myeloma. The clinical symptoms are such as thirst, nausea, vomiting, unconsciousness and constipation.
 
Anemia: Anemia with mainly due to the infiltration of myeloma cells into the bone marrow, the secretion of hematopoietic cytokines IL-6 and IL-1 by the tumor cells, and the decrease of Erythropoietin(EPO) caused by renal function damage. About 2/3 of the patients suffered from anemia, which manifested as fatigue, dizziness, weakness and tachycardia.
 
Renal insufficiency – Renal impairment mainly due to abnormal proteins, dehydration and hypercalcemia produced by myeloma cells. Creatinine clearance decreased occurs in 50% of patients. Renal insufficiency occurs in 20-40% of newly diagnosed patients. 3-12% of patients need dialysis. Renal insufficiency is one of the high-risk factors, which should be poor therapeutic effect, drug resistance, short survival and poor prognosis.
 
Infection - Acute bacterial infection may be the initial symptom of MM, in which pneumonia is most frequent, followed by urinary tract infection. The pathogens are mainly pneumococcus, Hemophilus influenzae, herpes simplex virus, etc, that is more common in patients with IgG type MM or with high M protein, renal insufficiency. Meanwhile. The infection is an important complication in the course of treatment, as the main causes of death for MM.
Treatment
Multiple Myeloma is incurable disease, but some treatments can contribute to alleviate symptoms and improve quality of life. At present, many new drugs for multiple myeloma have been developed and evaluated in clinical practice. New drugs have significantly prolonged the survival of patients. The following are commonly used treatment drugs for multiple myeloma patients.          
1.Proteasome inhibitors (PIs): The mechanism is to disrupt the normal degradation of proteasomes to intracellular proteins, leading to cell cycle arrest, promoting cell apoptosis and inhibiting angiogenesis.          
2.Immunomodulating drugs (IMiDs): whose mechanisms include: (1) promoting apoptosis of neovascular cells, inhibiting angiogenesis and cell adhesion, then inhibiting the protective effect of bone marrow microenvironment on MM cells; (2) enhancing immune reaction of natural killer (NK) cells to MM cells and stimulate anti-myeloma effect; (3) Co-stimulating CD4 + and CD8 + T cells through phosphorylation of CD28. To enhance its immune response to MM cells.
3.Monoclonal antibodies: The specific monoclonal antibodies against clonal plasma cell surface antigens, which have been used in clinical practice. The treatment of antibodies is more targeted and has good toxicity and tolerance compared with conventional drugs, which has become an important trend in the treatment of MM.
4.Histone deacetylase inhibitors (HDACi): It mainly inhibits the acetylation of histones and non-histones to control tumor progression.             
 
These drugs can be used alone or in combination with standard chemotherapy as a further treatment option for multiple myeloma.
For more information see your Doctor or Healthcare Professional.

 
1.  Nijhof IS, van de Donk NWCJ, Zweegman S, et al. Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update[J]. Drugs. 2018;78(1):19-37.
2.  NCCN Guidelines® Multiple Myeloma. Version 2.2019. November 2018
CP-87242 Approved date 2019-5-8