Multiple myeloma

1. MULTIPLE MYELOMA.
• Multiple myeloma (MM) is a plasma cell malignancy in
which monoclonal plasma cells proliferate in bone marrow,
resulting in an overabundance of monoclonal paraprotein
(M protein), destruction of bone, and displacement of other
hematopoietic cell lines.
• MM accounts for 10% of all hematologic cancers.[
• The median age at diagnosis of MM is 69 years. Less than
14% of patients are younger than 55 years, and only about
3% are younger than 45 years.

2. ETIOLOGY.
1.Genetic Predisposition: Multiple myeloma has a genetic component,
and individuals with a family history of the disease are at a slightly higher
risk. Specific genetic mutations, such as alterations in genes like TP53 and
MYC, have been associated with an increased risk of developing myeloma.
2. Plasma Cell Mutations: The development of multiple myeloma is often
initiated by genetic mutations in plasma cells (a type of white blood cell).
These mutations can cause these cells to become cancerous and multiply
uncontrollably.
3.Age: Myeloma is more common in older adults, with the risk increasing
significantly after the age of 65. The accumulation of genetic changes over
time may contribute to its development.
4. Environmental Factors: While the exact environmental triggers are
unclear, exposure to certain chemicals and toxins, such as pesticides and
herbicides, may be associated with a slightly increased risk.
5.Radiation Exposure: High levels of radiation exposure, such as those
experienced during nuclear accidents or certain medical treatments, have
been linked to an increased risk of developing myeloma.
6. Immune System Dysregulation: Disorders that weaken the immune
system, such as HIV/AIDS, may increase the risk of myeloma. A
compromised immune system may not effectively control the growth of
abnormal plasma cells.

3. PATHOPHYSIOLOGY.
• Abnormal Plasma Cell Growth: Multiple myeloma
begins when a single plasma cell in the bone marrow
undergoes genetic mutations, causing it to replicate
uncontrollably.
• Monoclonal Proliferation: These abnormal plasma cells,
also known as myeloma cells, produce identical copies
of themselves, leading to the proliferation of
monoclonal (identical) plasma cells.
• Bone Marrow Infiltration: The accumulation of
myeloma cells in the bone marrow disrupts the normal
production of blood cells, leading to anemia,
leukopenia (low white blood cell count), and
thrombocytopenia (low platelet count).

4. PATHOPHYSIOLOGY.
• Monoclonal Protein Production: Myeloma cells secrete monoclonal
immunoglobulins or M proteins, which can be detected in the blood and
urine. These proteins can lead to complications such as kidney damage.
• Bone Lesions: Myeloma cells also interact with bone cells, causing
osteoclasts (cells that break down bone) to become overactive, leading to
bone destruction and the development of lytic bone lesions. This can
result in bone pain and an increased risk of fractures.
• Hypercalcemia: The release of calcium from damaged bones can lead to
hypercalcemia, causing symptoms like fatigue, confusion, and kidney
problems.
• Renal Complications: Monoclonal proteins can accumulate in the kidneys,
impairing their function and potentially causing renal failure.
• Immunosuppression: Myeloma cells can suppress the immune system,
increasing susceptibility to infections.
• Hematological Abnormalities: The proliferation of myeloma cells can
crowd out healthy blood-forming cells in the bone marrow, leading to
reduced production of red blood cells, white blood cells, and platelets.
• Organ Damage: In advanced stages, multiple myeloma can affect various
organs, including the heart, lungs, and liver, due to the accumulation of
abnormal proteins and compromised immune function.

5. CLINICAL PRESENTATION.
1. Skeletal: Bone pain/tenderness,pathologic fractures and possible
spinal cord compression with vertebral involvement.
2.Constitutional symptoms: Weight loss ,malaise/fatigue ,fever.
3. Anemia : Anemia, which may be quite severe, is the most
common cause of weakness in patients with multiple myeloma.
4. Infection : Abnormal humoral immunity and leukopenia may lead
to infection. Pneumococcal organisms are commonly involved, but
shingles (ie, herpes zoster) and Haemophilus infections are also
more common in patients with MM.
5. Hypercalcemia: Confusion, somnolence, bone pain, constipation,
nausea, and thirst are the presenting symptoms of hypercalcemia.
6. Hyperviscosity: Hyperviscosity may be associated with a number
of symptoms, including generalized malaise, infection, fever,
paresthesia, sluggish mentation, and sensory loss. Patients may
report headaches and somnolence, and they may bruise easily and
have hazy vision. Patients with MM typically experience these
symptoms when their serum viscosity is greater than 4 times that of
normal serum.

6. DIAGNOSIS.
Laboratory workup
1. CBC: Anemia (normocytic)thrombocytopenia,leukopenia.
2. Blood chemistry panel: to measure various substances in
the blood, such as calcium levels (elevated in myeloma),
kidney function (creatinine and blood urea nitrogen), and
other electrolytes.
3. Serum Protein Electrophoresis (SPEP): This test identifies
the presence of abnormal proteins in the blood, often
referred to as M proteins or monoclonal proteins. Elevated
levels may indicate multiple myeloma.
4. Immunoglobulin Levels: Measurement of immunoglobulin
levels, including IgG, IgA, and IgM, can help identify
abnormalities in antibody production.

7. DIAGNOSIS.

8. TREATMENT.
1.Chemotherapy: Chemotherapy drugs, often combined in
regimens, are used to kill or control myeloma cells. Common drugs
include bortezomib, lenalidomide, and dexamethasone. High-dose
chemotherapy may be followed by autologous stem cell
transplantation in eligible patients.
2.Immunomodulatory Drugs: Drugs like lenalidomide and
pomalidomide help modulate the immune system's response and
can be used as part of the treatment regimen.
3. Monoclonal Antibodies: Monoclonal antibodies such as
daratumumab, elotuzumab, and isatuximab can target specific
proteins on myeloma cells, enhancing the immune system's ability
to recognize and destroy them.
4. Proteasome Inhibitors: Medications like bortezomib and
carfilzomib inhibit proteasomes in myeloma cells, disrupting their
function and leading to cell death.
5.Corticosteroids: Drugs like dexamethasone are often used to
reduce inflammation and control myeloma-related symptoms.

9. TREATMENT
6.Stem Cell Transplantation: In eligible patients, high-dose
chemotherapy followed by autologous stem cell
transplantation (using the patient's own stem cells) can be
an option to achieve deeper remissions.
7.Targeted Therapies: Newer targeted therapies, like
selinexor and belantamab mafodotin, are being used or
studied in clinical trials for their effectiveness against
multiple myeloma.
8.Radiation Therapy: Radiation may be used to relieve bone
pain caused by myeloma-related bone lesions or to target
localized plasmacytomas.
9. Supportive Care: This includes managing symptoms and
complications associated with multiple myeloma, such as
anemia, infections, kidney problems, and bone health.

10. DDX
1.MGUS (Monoclonal Gammopathy of Undetermined
Significance).
2. Primary Amyloidosis.
3.Chronic Lymphocytic Leukemia
4. Lymphoma.
5. Metastatic cancer.
6. Osteoporosis.
7. Sarcoidosis

11. COMPLICATIONS.
1. Bone marrow failure.
2. Hypercalcemia.
3. Bone lesions.
4. Renal impairment.
5. Anaemia.
6. Neuropathy.
7. Hyperviscosity Syndrome.