Multiple Myeloma
What is Multiple Myeloma?
• Multiple myeloma is a type of cancer of the plasma cells (a type of
white blood cell which are responsible for producing antibodies of
immune system) of the bone marrow.
• In multiple myeloma, the plasma cells undergo
a malignant transformation and become cancerous.
• Multiple myeloma is often referred to simply as myeloma, Kahler's
disease or plasma cell neoplasm.(Neoplasm is an abnormal growth
of tissue which, if it forms a mass, is commonly referred to as
a tumor)
T Lymphocytes vs B Lymphocytes
In the blood, there are cells and plasma. The main two types of cells
are Red Blood Cells (RBC) and White Blood Cells (WBC). RBC is
mainly for carrying the oxygen and WBC is for defence mechanism.
Again there are two types in white blood cells.
The cells that contain granules in the cytoplasm (granulocytes) and
that not having granules in the cytoplasm (agranulocytes).
• Granulocytes also divided in to two; lymphocytes and monocytes.
Lymphocytes are similar in appearance, but they have different
functions. According to the functions, lymphocytes are divided in
to T lymphocytes and B lymphocytes. Both are important to fight
against the infections. The T lymphocytes will mature in thymus.
B lymphocytes are mainly in the lymph nodes. T lymphocytes can
kill the infected cells (Cyto toxic). Some of the T lymphocytes are
helper cells
• B lymphocytes usually secrete the antibodies. The antibodies will
neutralize the antigen. Antibodies are specific to the infection.
That means different infections will produce different antibodies.
The B cells can secrete antibodies when it is activated. When B
cells are secreting antibodies, it will be named as plasma cells.
What happens to plasma cell during
multiple myeloma?
• The myeloma cells stop making different forms of protein in response to
the immune system's needs and instead start to produce a single
abnormal type of protein sometimes termed a monoclonal or M protein.
• Multiple myeloma plasma cell populations (plasmacytomas) accumulate
in the bone marrow and erode the hard outer shell or cortex of the bone
surrounding marrow, weakening the bones which leads to lytic bone
lesions causing pain and even breaks or fractures.
(Plasmacytoma is a plasma cell dyscrasia in which a plasma
cell tumor grows within soft tissue or within the axial skeleton)
What causes multiple myeloma?
• The exact cause of malignancy of plasma cells in multiple myeloma
is unknown but the causes related to multiple myeloma may include
toxic chemicals, radiation, some viruses or immune disorders.
Multiple Myeloma: Epidemiology
• Second most common hematological malignancy
• Incidence and rates:
– 1% of all cancers
– US incidence: 19,900 new cases per year
– US prevalence: 100,000 patients
– Deaths: estimated 10,790 per year
• More than 80% of affected patients >age 60
• Affects slightly more men than women (1.6:1).
Clinical course of multiple myeloma
Survival (years)
0 1 2 3 4 5
Diagnosis to death 3–4 years
Relapsed disease
• Transient response 1–2 years
to therapy
Relapsed and refractory
• Resistant to all therapy 6–9 months
• Universally fatal
Risk factors
• Researches have suggested several risk factors in case of multiple
myeloma that includes, genetic abnormality such as c-Myc oncogenes
(This leads to the increased expression of many genes, some of which
are involved in cell proliferation)
• Environmental exposures to herbicides, insecticides, benzene, hair dyes,
and radiation but definitive data is lacking.
• Inflammation and infection have been suggested but again not proven
to cause multiple myeloma.
Risk factors Contd…
• However, a benign proliferation of a plasma cell can result in a
situation where a monoclonal antibody is produced in high
amounts (but not as high as seen with multiple myeloma). This
result is termed monoclonal gammopathy of unknown or
undetermined significance (myeloma-related plasma cell
neoplasm).
Symptoms and Signs
The symptoms include :
Anemia
Bleeding
Nerve damage
Skin lesions (rash)
Enlarged tongue (macroglossia)
Bone tenderness or pain, including back pain
Weakness, fatigue or tiredness
Infections
Pathologic bone fractures
Back pain
Spinal cord compression
Kidney failure and/or other end-organ damage
Loss of appetite and weight loss
Constipation
Hypercalcemia
Leg swelling
Diagnosis
• Diagnosis of multiple myeloma includes bone marrow aspiration,
biopsy most commonly from the large bones of the pelvis,
cytogenetic test, blood test and urine test, serum free light chain
assay and fluorescence in situ hybridization (FISH) test, and other
routine test.
Bone Marrow Aspiration needle
What are the stages of multiple
myeloma?
There are four stages of multiple myeloma including:
Smoldering: multiple myeloma with no symptoms
Stage I: early disease with little anemia, relatively small amount of M
protein and no bone damage
Stage II: more anemia and M protein as well as bone damage
Stage III: still more M protein, anemia, as well as signs of kidney
damage.
Common Sites for Bone Involvement
Skull
Spine
Thoracic
Lumbar
Pelvis
Long bones
Spinal cord – compression
can occur
Multiple Myeloma: Typical “Punched Out”
Lesions
Clinical features
Clinical features
Medical treatment
• There is no known medical treatment that cures multiple myeloma.
However, there are methods to decrease the occurrence and severity
of symptoms and prolong life.
• The choices for treatment(s) often include combinations of drugs
such as pills and intravenous injection.
• There may be a role for high-dose chemotherapy followed by the
administration of bone marrow stem cells called a stem cell
transplant or auto transplantation.
Drugs used for treatment
• There are many drugs used to treat multiple myeloma. The following
drugs are used often in combination with dexamethasone, sometimes
orally or by IV, depending on the patient's individual disease status:
Dexamethasone Bortezomib
Lenalidomide Pamidronic acid
Zoledronic acid Melphalan
Carfilzomib Daratumumab
Elotuzumab
Survival rate for multiple myeloma
• The prognosis of multiple myeloma is variable, depending on the
approximate stage and response to therapy. The median survival
rate, beginning at the point of first treatment according to the
American Cancer Society (ACS), according to stage of the disease is
as follows:
Stage I, 62 months
Stage II, 44 months
Stage III, 29 months
Latest research on multiple myeloma Contd…
• Researchers have used this method to provide multiple
myeloma patients with uncontaminated stem cells successfully
preventing relapse of multiple myeloma due to contaminated
stem cell cultures.
Myxoma Virus
Thank
you
