Multiple Myeloma (Free Trial)

Practice this case based on how you are assessed in your OSCEs, and use the relevant sections for general revision. 🤓

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Doctor Instruction:

You are a doctor working in a haematology clinic. Your next patient is Luffy D Piece – a 56-year-old man who has been referred by General Practice using a 2-week wait referral – querying haematological cancer. This patient presents with easy bruising with a urine test showing "light chain proteins". Please take a history and perform an appropriate examination.

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Patient History:

Your name is Luffy D Piece – 56-year-old gentleman – retired.

You came in today due to bruising around the surface of your tummy and arms, which started one month ago. Since then, this has been gradually getting worse. You are not bleeding anywhere else as far as you are concerned e.g. stool, urine…etc.

You also noticed worsening back pain behind your chest – describing it as a constant dull ache – a 5/10 pain score that sometimes can wake you up at night. This is not the only thing that is causing you trouble falling asleep! You also have night sweats and have been waking up in the middle of the night to urinate more often than usual. You always feel thirsty.

You feel tired, but you think this is because of the poor sleep you have been getting – averaging only around 3-4 hours a night. You have lost a bit of weight in the past month, around 2 kg. However, you have a low appetite and haven’t eaten the same amount as usual. You are constipated and currently taking a laxative you got from the chemist, which only improved slightly.

No changes in vision. No headache, No dizziness. No confusion. No shortness of breath. No chest pains. No fever.

Ideas, Concerns, Expectations:

• You have no idea what is going on. Everything feels so weird. You do not feel like yourself anymore - you have never experienced anything like this. You are concerned as your GP mentioned "cancer" needs to be ruled out. You do not want to die yet! You hope to find out what is going on and get treatment as soon as possible.

Past Medical History:

• Heart Failure, Hypercholesteremia, Obesity

Drug History:

• Furosemide, Movicol (laxative)

Family History:

• Hypertension

Social History:

• Retired but used to work as an on-site petroleum chemical engineer, ex-smoker, rarely drinks alcohol, lives alone in a Bungalow, independent.

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Examination Findings:

• Random patterned bruising around the surfaces of arms and abdomen with no active bleeding on general inspection.

• Signs of dehydration- reduced skin turgor, increased CRT, dry mucous membrane.

• Palmar erythema.

• Mild pitting oedema at ankles.

• Calves are soft and non-tender.

• Spinal tenderness at the thoracic region

• No other abnormal findings otherwise on examination.

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Differentials:

1. Multiple Myeloma (MM)

2. Monoclonal gammopathy of undetermined significance (MGUS)

3. Solitary plasmacytoma (due to localised bone pain)

4. Amyloid light-chain (AL) amyloidosis

5. B-cell non-Hodgkin’s lymphoma

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Investigations:

Bedside:

• Observations

• Urine electrophoresis to detect free monoclonal light chain paraprotein (Bence Jones Protein)

Bloods:

• FBC (normocytic anaemia)

• Bone Profile (hypercalcaemia, hyperalbuminemia)

• U&Es (can show impaired renal function and dehydration)

• ESR/plasma viscosity (raised)

• Coagulation screen (bruising/bleeding)

• Serum-free light chain assay (raised)

• Serum immunoglobulin (non-myelomatous Ig can be suppressed, but myelomatous Ig is raised)

• Serum protein electrophoresis (shows the raised type of myeloma proteins, especially in active/smouldering MM)

• Serum beta2-microglobulin (for staging MM)

• Serum/urine immunofixation (identify paraprotein Ig subtype in MM)

• LDH (higher levels indicate extensive disease)

• Hba1c/ glucose (due to polyuria/polydipsia/weight loss)

• Hepatitis screen / HIV screen before starting myeloma treatment

Imaging:

• Skeleton Survey

• MRI/CT (full body)

• Consider XR when indicated– patchy/ thin bones, osteolytic/punched-out lesions, pathological fractures, collapsed vertebral body, raindrop skull…etc.

Special tests:

• Bone marrow aspirate and biopsy with plasma cell phenotyping (confirm the diagnosis of myeloma and assess monoclonal plasma cell infiltration)

• Consider cytogenetic analysis and fluorescence in situ hybridisation (FISH) (prognostic test with therapeutic implications)

• Consider mass spectrometry (detects the presence of a paraprotein)

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Management:

Conservative:

• Simple Analgesia such as paracetamol, opioids. Adjuvant: amitriptyline, carbamazepine, gabapentin.

• Consider alternatives: relaxation, aromatherapy hypnotherapy

• Hydration

• Emotional/psychological support for patients, relatives, and carers.

Medical:

• Treatment guided by haematology and oncology specialists

• Non-chemotherapy regimens - a combination of dexamethasone and immunomodulatory agents e.g. Bortezomib/carfilzomib, thalidomide/lenalidomide

• VTE prophylaxis whilst on thalidomide due to increased risk of thrombus – aspirin / LMWH/ DOAC

• Conventional chemotherapy regime: a combination of dexamethasone, immunomodulatory agents e.g. bortezomib, and chemotherapy e.g. cyclophosphamide/ doxorubicin/ vincristine

• Radiotherapy for bone lesions and bone pain

• Orthopaedic surgery for stabilising bone or treating fractures

• Cement augmentation – cement injection in vertebral fractures/ lesions to improve spine stability and pain

• Stem cell transplantation (melphalan is used for the standard conditioning regimen before stem cell transplant)

• Treat any complications of myeloma e.g. infection, renal failure, spinal cord/nerve root compression, neuropathy…etc.

• Regular monitoring of bloods and review for symptoms and treat relapsing episodes.

Secondary Prevention:

• Pneumococcal/ flu vaccination, consider anti-viral prophylactics, avoiding contrast dyes in poor renal function, treating infection promptly, bisphosphonate/denosumab in myeloma bone disease (suppress osteoclast activity).

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Viva Questions:

Explain the pathophysiology of multiple myeloma.

Multiple myeloma is a cancer of plasma cells in the bone marrow. Abnormal proliferation leads to tumor formation, bone destruction, and monoclonal immunoglobulin production. This disrupts normal blood cell production, causes bone lesions, and compromises immune function. Complications include anemia, renal impairment, and hypercalcemia.

What are the differences between multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), and smouldering myeloma?

Multiple Myeloma (MM): Symptomatic cancer with organ damage, specific diagnostic criteria, and a progressive course.

Monoclonal Gammopathy of Undetermined Significance (MGUS): Asymptomatic precursor condition with a low risk of progression to myeloma.

Smoldering Myeloma: Intermediate stage between MGUS and myeloma, characterized by higher M protein levels and/or clonal plasma cells with a risk of progression.

Which immunoglobulins are most commonly affected in myeloma?

In multiple myeloma, the most commonly affected immunoglobulins are IgG and IgA. The overproduction of these abnormal antibodies contributes to the disease's complications.

What organs can be affected by myeloma? What are the complications of myeloma?

• Bone: Causes lytic lesions, pain, and fractures.

• Bone Marrow: Reduces blood cell production, causing anemia, infections, and bleeding.

• Kidneys: May result in renal impairment.

• Immune System: Weakens immunity, increasing infection risk.

• Nervous System: Can cause neurological symptoms.

• Blood Clotting: Raises the risk of clotting disorders.

• Other Organs: Rarely affects the liver, lungs, and gastrointestinal tract.

What are the XR findings you get from myeloma bone disease?

• Lytic Lesions: Lytic lesions are holes or punched-out areas in the bone caused by the destruction of bone tissue. These lesions can be seen on X-rays and are a hallmark of myeloma bone disease. They often appear as radiolucent (dark) areas on the X-ray.

• Multiple Lesions: Myeloma bone disease typically affects multiple bones, and X-rays may reveal the presence of multiple lytic lesions throughout the skeleton. The distribution of these lesions can be widespread.

• Pathological Fractures: Weakened bones due to myeloma can lead to pathological fractures, which are fractures that occur in weakened bone without significant trauma. X-rays may show evidence of fractures that are not associated with a specific injury.

• Bone Density Changes: X-rays may show changes in bone density, and affected bones may appear less dense or thinner than normal.

• Soft Tissue Masses: In some cases, myeloma can cause the formation of soft tissue masses or tumors adjacent to bones. These masses may be visible on X-rays.

What are the signs of hypercalcaemia?

• Excessive Thirst and Urination: Increased calcium levels can lead to dehydration, causing excessive thirst and frequent urination.

• Fatigue and Weakness: Hypercalcemia can cause generalized weakness and fatigue.

• Nausea and Vomiting: Elevated calcium levels may lead to nausea and vomiting.

• Constipation: Hypercalcemia can affect the digestive system, leading to constipation.

• Abdominal Pain: Some individuals with hypercalcemia may experience abdominal pain, often in the area around the stomach.

• Loss of Appetite: A decreased appetite is a common symptom of hypercalcemia.

• Muscle and Joint Pain: Elevated calcium levels can affect muscles and joints, leading to pain and discomfort.

• Confusion or Cognitive Impairment: Severe hypercalcemia may impact cognitive function, leading to confusion, difficulty concentrating, and memory problems.

• Excessive Sleepiness: Some individuals with hypercalcemia may experience drowsiness or excessive sleepiness.

• Depression or Emotional Changes: Changes in mood, including depression or anxiety, may occur.

• Bone Pain: Hypercalcemia can affect the bones, leading to pain and increased risk of fractures.