Types of multiple myeloma
"When I learned that I was diagnosed with ‘smoldering (asymptomatic, indolent) myeloma’ my immediate response was when and where are we going to start the treatment. The doctor’s response was, that for the time being, they were just going to observe me! And regardless of my diagnosis, life still goes on."
Results of the blood, bone marrow and urine test in combination to other diagnostics procedures (X-rays and other imaging diagnostics, etc.) reveal the type of multiple myeloma. The majority of patients of multiple myeloma cases, approximately 65 %, belong to the subclass IgG. Patients are characterized by clonal and non-functional antibodies (protein) excreted by plasma cells. The second most common subclass in patients is subclass IgA. Subclasses IgM, IgD and IgE are rare. But multiple myeloma is not the only plasma cell disorder. There are other similar diseases as well. The clinical picture of a multiple myeloma can vary tremendously. Some patients suffer from symptoms of a ‘smoldering, indolent’ disease which does not require immediate treatment. But with others, a sudden onset of multiple myeloma can take an aggressive turn targeting bones, kidneys and cause organ failure.
Typically the multiple myeloma develops from a previous ‘irregularity/disease’ called MGUS or ‘monoclonal gammopathy of undetermined significance’. The onset of this disease is more common in older persons (3 % of people older than 70 years, with age the percentage increases). It is a benign and constrained overgrowth of plasma cells which produce a relatively low amount of M-protein (monoclonal protein). Such a condition doesn't require treatment, but patients do need to be regularly monitored and observed. Probability that MGUS will develop into multiple myeloma increases by 1 % for every additional year (e.g. a 60-year-old patient with MGUS will have a 20 % chance of developing multiple myeloma when he turns 80).
Physicians distinguish between various types of multiple myeloma.
Asymptomatic multiple myeloma
This type of multiple myeloma is better known by the name ‘smoldering (asymptomatic, indolent) myeloma’. The concentration of M-protein and the share of plasma cells in the bone marrow is higher in comparison to patients with MGUS, but there are no signs which would suggest that the disease is the cause of clinical symptoms and organ damage. Patients are not anemic at this stage, and don’t have hypercalcemia, there are no changes to the bones, nor are there any signs of impaired renal function.
Asymptomatic multiple myeloma doesn't require any treatment. Nonetheless, patients must be regularly monitored as progression to symptomatic multiple myeloma occurs over time in most patients. And this disease does require treatment.
Symptomatic multiple myeloma
Symptomatic multiple myeloma differs from asymptomatic in the onset of at least one symptom characteristic for this disease (but could entail all): anemia, hypercalcemia, skeletal changes –osteolysis, or impaired renal function. If that is the case, treatment shall be started immediately.
Solitary plasmocytoma is a condition where plasma cells accumulate only in one area of the body; this doesn't have to necessarily be in the bone marrow, and the bone marrow is not affected. This mass formation is common, for example, in the head or throat region where glands and lymphatic tissue is present. It could also manifest itself in an isolated vertebra. We distinguish between the two according to location: skeletal and non-skeletal. The patient does not have anemia, hypercalcemia, there are no discernible skeletal changes, and renal function is not impaired.
In the early stages, solitary plasmacytoma is treated with surgical intervention and local radiation therapy using ionizing rays (radiotherapy). With patients suffering from this type, there is a 50 per cent probability that it will progress to multiple myeloma, although sometimes the process takes longer than 15 years.
Only in 1 % of multiple myeloma patients, monoclonal antibodies or excessive levels of serum free light chains cannot be detected. Nevertheless, these patients have > 10 % share of clonal plasma cells in the bone marrow and all clinical disease symptoms. Although these patients have a lesser risk of renal complications, all other symptoms are comparable to classic multiple myeloma symptoms. This makes disease diagnostics more difficult as bone marrow examination is necessary.
A solitary mass accumulates outside the bone or bone marrow with this type of multiple myeloma. It can affect any part of the body, but most probable areas are the upper respiratory tract where there is a lot of lymphatic tissue. Typically monoclonal antibodies in blood cannot be detected. An increase of plasma cell numbers in bone marrow cannot be detected as well. Patients also have no clinical problems arising from the disease itself, except for those associated with the tumor growth.
Extramedullary plasmacytoma progresses into multiple myeloma with 15 % of patients in comparison to 50 % of patients with solitary plasmacytoma. This type of multiple myeloma normally requires only surgical intervention and local radiation treatment with ionizing rays.
Plasma cell leukemia
Plasma cell leukemia is a condition where cancer plasma cells can be found in the patient’s peripheral blood, and outnumber leukocytes by 20 %. This disease can affect anyone, even patients already suffering from multiple myeloma. Patients with plasma cell leukemia need urgent treatment and the long term prognosis is not favorable.
The course of multiple myeloma
Despite the fact that the treatment is successful for the majority of patients, this disease has a high relapse rate. The goal of the treatment is therefore to prevent relapse, reduce complications and extend lifespan. If the disease relapses, the treatment should be repeated. Now our aim is to reach a complete response rate when treating multiple myeloma with the new drugs. This will significantly impact any possible complications arising from the disease and extend the survival rate of patients treated.
AL amyloidosis – light-chain amyloidosis
15 to 20% of patients who suffer from multiple myeloma can have a subdued AL amyloidosis. This means that clonal plasma cells produce excess free light-chains which in turn form a special amorphous protein called amyloid. This protein accumulates in all organs of the body except for the central nervous system. It accumulates in the heart, respiratory system, kidneys, peripheral nervous system, gastro-intestinal tract, etc.
Patient’s clinical signs include signs of heart failure and kidney failure (they in turn secrete large amounts of protein), shortness of breath, diarrhea, weight loss, tingling sensations and numbness of hands and feet, light-headedness, it can result in loss of consciousness and carpal tunnel syndrome. Diagnosis is determined histologically. This means that a part of affected tissue has to be microscopically examined. Fat is usually affected; thus a biopsy of fat can be carried out. Associated AL amyloidosis is treated by treating multiple myeloma. By effectively treating multiple myeloma, clinical issues arising from amyloidosis subside as well.
Even if the patient isn't suffering from multiple myeloma, plasma cells can still produce amyloid and after a clonal sample too. This is also known as AL amyloidosis. Organ impairment, clinical picture and diagnostic procedures are the same with patients suffering from multiple myeloma with accompanying AL amyloidosis. Concentration of M protein is elevated slightly with patients suffering from amyloidosis the same way it is with patients suffering from MGUS (monoclonal gammopathy of undetermined significance), a predecessor to multiple myeloma. An elevated level of protein in urine and elevated hormone levels in the blood which point to heart failure (BNP) are characteristic of the disease.
AL amyloidosis is treated with the same methods as multiple myeloma, even with autologous HSCT if the patient’s condition allows it. The aim of the treatment is to suppress plasma cell clones which excrete amyloid and therefore prevent its deposition in the tissues.