What is Myeloma?
A Type of progressive malignant cancer that initates in white blood cells in the bone marrow (that is the spongy inner part of the bones that is responsible to produce different types of blood cells), speciafically plasma cells.
Plasma cells are matured B-cells that normally produce antibodies (aka immunoglobulines) to fight infection. When there is some changes in the DNA while plasma cells are produced which leads to abnormal plasma cells being produced (known as myeloma cells). These abnormal cells produce abnormal type of antibodies (aka paraproteins , monoclonal spikes) which are unable to fight infections. They also produce these paraprteins in excess which reduce the amount of antibodies that are capable of fighting infections.
Myeloma also known as multiple myeloma, effects multiple including the bones, kidneys, blood, and immune system.
Symptoms
Although most people are symptoms free in the early stages of disease and tend to get diagnosed after a routine blood test ,however, as the disease progresses, people tend to get symptoms.
Signs and symptoms of myeloma may include;
Bone pain (mainly in back, hips, shoulders and ribs)- as myeloma initiates in the bones, myeloma cells can grow and damage the bone, they further cause thinning of the bones (osteoporosis) these cause the bones to be more prone to breaking aswell. Bone pain is experienced by up to 70% of myeloma sufferers and is described as a dull or aching pain.
Bone Fractures: as the bones become weak they can break easier. The most effects bones are the spine, arms and legs.
Infection susceptibility: As myeloma progress, there will be less healthy white blood cells produced and capable of functioning therefore, fighting bacterial and viral infections would be more difficult for the body and it takes it longer for the body to clear infections. More frequent infections would also occur.
Anaemia: more than 50% of patients with myeloma are effected. As teh red blood cells are also produced in bone marrow, myeloma cells disrupt their production as the disease progresses and causes low levels of blood cells (anaemia). This further leads to tiredness, weakness and breathlessness.
High calcium levels in the blood (hypercalcinemia)
The affected bones tend to release too munich calcium into the blood aswell which lead to symptoms such as:
- Extereme thirst
- Excessive urinating
- Kidney problems (in some cases kidney failure)
- Loss of appetite
- Confusion
- Severe constipation
Hypercalcaemia is treated by using hydration and use of bisphosphonates.Bisphosphantes (such as alendronic acid) which reduce calcium level by increaing their the absorption of calcium to the bones (increase bone mineral density).
The weaknenning of hte bones in the spine also can lead to spinal cord compression, as the spine gets weaker the bones can collapse and put pressure on the nerves in the spine. This leads to sudden back pain , pins and needles, weakness in lower extremities, and difficult controlling bowel and bladder movement. This requires urgent medical attention as permanent nerve damage can occur.
Hyperviscosity syndrome
Due to increase levels of antibodies circulating around the body, the blood tends to be more viscous (thickens) than usual. This can lead to problems such as blurred vision ,headaches ,and dizziness.
Plamsopheresis is a process that removes the proteins produced by myeloma cells and tend to help with hypervisocity of the blood.
Kidney problems
As the paraproteins produced by myeloma cells pass through the filters in the kidney (known as glomeruli) , they can sometimes join and combine with the other normal proteins that are already in the glomeruli and block tubules ( pipes ) and prevent flow of fluid in hte kidneys which leads to kidney damage. These abnormal proteins can also cause inflammatory reaction in the kidneys aswell that damages the kidneys further. Signs of kidney failure include; weigh loss, swollen ankles , shortness of breath , itchy skin and hiccups that won't go away.
Causes and risk factors
The exact cause of multiple myeloma is still unknown. However there are factors that increase the risk of getting multiple myeloma.
Gender: Myeloma effects men slightly more than women, where men have a life time risk of 1 in 83 and women have a 1 in 116 of getting myeloma.
Age: myeloma is very rare for anyone under age of 40 (only 2% of cases) and most commonly occurs in over 60s.
Obesity: Overweight or obese people tend to have a higher risk of multiple myeloma.
Causes
Lowered immunity: people who take immunosuppresants medications after an organ transplant have a slight increase in risk of getting myeloma (however the risk is extremely low).
Ethnicity: myeloma is more common in black ethinic population than in white ethnic group. Asians have the lowest risk of myeloma. It is important to note that studies use broad ethnic groups in their research so the rate could vary within a subgroups of each ethnic group.
Exposure to certrain chemical compounds: exposure to some chemical compounds such as benzene are linked to multiple myeloma.
Monoclonal gammopathy of undetermined significance (MGUS):
MGUS is a non-cancerous condition where the body produces abnormal proteins. MGUS affects plasma cells in the bone marrow. 1 in 100 people who suffer from MGUS develop myeloma.
What is thalidomide?
A drug developed in 1950s by a german pharmaceutical company to treat nausea and vomiting (morning sickness) in pregnant women. The drug was distribtued among 49 countries.
Even though it deemed safe in pregancy at the time, the drug is responsible for tetratogenic (a drug that disturbs development of fetus or embryo) deformetities of children born in whom their mother used thalidomide while preganant. It is estimated that around half of these affected babies born died within months of being born and the rest had to suffer the deformities caused by the drug.
Thalidomides dark history however, has not effected its use in treating certain disease, for example it is currently used as unlicensed treatment of skin complication of leprosy and currently used as a first line treatment for multiple myeloma.
Newer drugs derived from thalidomide
Analogues of thalidomide are named maily pomalidomide and lenalidomide where they are slightly different in terms of structure to thalidomide. These analogues tend to be more potent with differnet toxicity profiles.
When is it used?
Thalidomide is often used as a first line treatment for myeloma alongside high dose dexamethasone (a potent steroid, as it reduces inflammation and reduces pain) and bortezomib (proteasome inhibitor that triggers programmed cell death).pomalidomide and lenalidomide are often used in relapsed multiple myeloma.
How does thalidomide work?
Thalidomide is an immunomodulatory drug (drugs that modfiy the immune system response) and it helps treating myeloma in several ways:
- Inhibitor of proliferation (multiplications) of myeloma cells
- Anti-angiogentic , where it prevents formation of new blood cells that supply nutrients and oxygen to cancerous cells /prevents their spread.
- Also activates certain pathways that leads to myeloma cells death.
How do you take thalidomide?
Thalidomide is mass produced in form of capsules(tablets, oral solution are also used by ordered from a special manufacturer where they produce these formulations on small scale). Thalidomide capsules are taken preferablliy at night (as they can cause drowsiness). Depending on the type of combination of the medication the person is on, thalidomide can be used from 1 capsule per night however, most commonly it is taken as 4 capsules at night (200mg).
Pregnancy and Thalidomide
As thalidomide and thalidomide analogues are tetratogenic, there are some precautions required for patients starting thalidomide. Firstly pregenecy must be excluded prior initiation of the treatment via a meically supervised pergenency test within 3 days of treatment. The pregenecy test is carried out every 4 weeks during the treatment and 4 weeks after the last dose. Furthermore, female patients that are capable of getting pregnant should use effective contraception for 4 weeks before and after (during treatment aswell) treatment.
Heterosexual males should also use condoms during treatment up utnil a week after their treatment as thalidomide is present in their semen (if their partner is of childbearing potential).
Side effects
Common
Most common side effects of thalidomide are ,
- Drownsiness and dizziness
- Malaise (general discomfort)
- Blurred vision
So patients on thalidomide are advised not to drive if they experience these symptoms.
Clinically significant side effects
- Thromboembolism: patients who have a high risk of thromboembolism for example smokers, are given medications to prevent their formation of a blood clot (thrombus).
- Peripheral neuropathy: This occurs when the nerves in hands ,feet, and arms are damaged where the patient feels numbness and burning sensations in the affected area. Patient who suffer previously suffered from this previously , thalidomide can exacerbate this.
- Rash, If a rash occurs, the treatment should be either stopped or its dose be reduced depending on the circumstance. Thalidomide is also associated with more serious skin reaction such as steven johnson syndrome and toxic epidermal necrolysis where requires hospitalisation and withdrawal of thalidomide.
Summary
Thalidomide is an old drug with a dark history,however, it can be used as treatment for of mulple myeloma and leprosy.
