After reading this note you will be able to describe the clinical presentation, perform a focused examination, interpret the key investigations and outline the immediate and definitive management of multiple myeloma, recognising local risk factors. All drug doses and local protocols must be checked against the Kenya MoH guideline and the hospital formulary.
Definition
Multiple myeloma (MM) is a clonal plasma‑cell malignancy characterised by uncontrolled proliferation of malignant plasma cells in the bone marrow, production of a monoclonal immunoglobulin (M‑protein) and associated organ dysfunction (CRAB: hyperCalcaemia, Renal failure, Anemia, Bone lesions).
Anatomy and physiology you need
| Structure | Normal role | Relevance in MM |
|---|---|---|
| Bone marrow | Hematopoiesis, plasma‑cell maturation | Site of clonal expansion → crowding out normal cells |
| Plasma cells | Produce polyclonal immunoglobulins | Malignant clone secretes monoclonal Ig, suppresses normal Ig |
| Skeletal system (trabecular bone) | Calcium reservoir, structural support | Osteoclast activation → lytic lesions, hypercalcaemia |
| Kidney (glomeruli & tubules) | Filtration, reabsorption | Light‑chain cast nephropathy, hypercalcaemia‑induced nephrocalcinosis |
| Immune system | Antigen defence | Immunoparesis → infections, especially opportunistic in HIV/TB settings |
Causes and risk factors
Most cases are idiopathic; however, several environmental and infectious factors prevalent in Kenya modify risk.
| Factor | Reason it matters in Kenya |
|---|---|
| Age > 60 y | Median age similar worldwide; increasing life expectancy |
| Male sex | Slight male predominance reported |
| HIV infection | Chronic immune activation, cytokine dysregulation, earlier onset |
| Chronic hepatitis B/C | Persistent inflammation may promote plasma‑cell dyscrasia |
| Tuberculosis | Long‑standing immune stimulation; co‑infection can mask MM symptoms |
| Malaria endemicity | Repeated immune activation may contribute, though data limited |
| Sickle cell disease | Chronic marrow stress and hemolysis create a proliferative environment |
| Autoimmune/rheumatic disease (e.g., SLE) | Persistent B‑cell activation |
| Occupational exposure (pesticides, petrochemicals) | Agricultural work common in rural Kenya |
| Family history of plasma‑cell disorders | Rare but acknowledged |
Pathophysiology
- Genetic hit → chromosomal translocations (e.g., t(11;14), t(4;14)) or hyperdiploidy
- Clonal plasma‑cell expansion → accumulation in marrow → suppression of normal hematopoiesis
- Monoclonal immunoglobulin production → excess free light chains (FLC) circulate
- FLC deposition in renal tubules → cast formation → tubular obstruction → renal failure
- Cytokine release (IL‑6, RANK‑L, MIP‑1α) → ↑ osteoclast activity & ↓ osteoblast function → lytic bone lesions & hypercalcaemia
- Immunoparesis → reduced polyclonal Ig → susceptibility to bacterial, viral (including HIV‑related) and fungal infections
- Anemia → marrow crowding + reduced erythropoietin → fatigue, dyspnoea
Overall cascade: Genetic lesion → malignant plasma‑cell clone → M‑protein & cytokine excess → CRAB organ damage.
Clinical features
| History element | Why it matters |
|---|---|
| Bone pain (especially back, ribs, pelvis) | Caused by osteolytic lesions and pathological fractures from plasma‑cell infiltration of marrow. |
| Pathologic fractures or recent trauma with minimal injury | Indicates structural weakening of bone; a red flag for myeloma‑related lytic disease. |
| Fatigue, weakness | Result of anaemia due to marrow replacement and reduced erythropoiesis. |
| Unexplained weight loss or night sweats | May reflect high tumour burden or concurrent infection (TB, HIV). |
| Recurrent infections (sinusitis, pneumonia, skin) | Immunoparesis from suppressed normal immunoglobulins; also common in HIV‑positive patients. |
| Renal symptoms (polyuria, nocturia, flank pain, edema) | Light‑chain cast nephropathy, hypercalcaemia‑induced diuresis, or obstructive uropathy from plasmacytomas. |
| Hypercalcaemia symptoms (constipation, polyuria, polydipsia, confusion) | Bone resorption releases calcium; high calcium can cause neuro‑cognitive changes. |
| Neurological complaints (numbness, tingling, back pain radiating to legs) | Spinal cord or nerve root compression by vertebral collapse or plasmacytoma. |
| Bleeding tendency (easy bruising, epistaxis) | Thrombocytopenia from marrow infiltration; also platelet dysfunction from paraprotein. |
| Past medical history (HIV, chronic TB, malaria, sickle‑cell disease, autoimmune rheumatic disease) | These conditions can alter immune status or cause chronic antigenic stimulation, modestly increasing myeloma risk in our setting. |
| Family history of haematological malignancy | May suggest inherited predisposition. |
| Medication history (alkylating agents, radiation exposure) | Known risk factors for plasma‑cell dyscrasias. |
Examination findings and their pathophysiological basis
| Finding | Explanation |
|---|---|
| Localized bone tenderness over spine, ribs, pelvis | Direct pressure on lytic lesions; may be the only sign of skeletal involvement. |
| Palpable mass (soft tissue plasmacytoma) | Extramedullary plasma‑cell proliferation; may be subcutaneous or in the nasopharynx. |
| Anemia signs (pallor, tachycardia) | Reduced red‑cell mass from marrow crowding. |
| Thrombocytopenia signs (petechiae, bruises) | Low platelet count or functional inhibition by paraprotein. |
| Hypercalcaemia signs (dehydration, dry mucous membranes, altered mental status) | Calcium excess leads to polyuria, volume depletion, neuro‑cognitive effects. |
| Renal signs (edema, hypertension, reduced urine output) | Cast nephropathy or light‑chain deposition causing renal insufficiency. |
| Neurological deficits (weakness, sensory loss, gait disturbance) | Compression of spinal cord/nerve roots by vertebral collapse or plasmacytoma. |
| Lymphadenopathy or hepatosplenomegaly – usually absent | Their presence would favour alternative diagnoses (e.g., lymphoma, infection). |
Differential diagnosis
| Condition | Points toward it | What separates it from multiple myeloma |
|---|---|---|
| Metastatic bone disease (breast, prostate, lung) | Bone pain, weight loss, older age | Imaging shows mixed lytic‑blastic lesions; tumour markers positive; no monoclonal protein. |
| Primary bone lymphoma | Localised bone pain, B symptoms | Biopsy shows lymphoid cells; PET‑CT avid; serum protein electrophoresis usually normal. |
| Osteomyelitis / TB of spine | Fever, night sweats, focal tenderness | Elevated inflammatory markers, positive cultures/CBNAAT; imaging shows sequestra, disc involvement. |
| Sickle‑cell disease bone crisis | History of sickle disease, episodic pain | Hemoglobin electrophoresis abnormal; crises triggered by dehydration, not associated with monoclonal protein. |
| Hyperparathyroidism | Hypercalcaemia, bone pain | Elevated PTH, renal stones; no monoclonal spike, bone changes are subperiosteal. |
| Waldenström macroglobulinemia | IgM paraprotein, hyperviscosity symptoms | IgM spike, no lytic bone lesions, often lymphoplasmacytic infiltration. |
| Chronic lymphocytic leukemia | Lymphocytosis, splenomegaly | Peripheral smear shows smudge cells; immunophenotype CD5+, CD23+; no significant bone lesions. |
Investigations
| Test | What it answers | Typical result in multiple myeloma |
|---|---|---|
| Serum protein electrophoresis (SPEP) + immunofixation | Presence and type of monoclonal (M) protein | Sharp M‑spike; immunofixation identifies IgG, IgA or light‑chain only. |
| Serum free light‑chain assay | Quantifies κ and λ free light chains, calculates ratio | Abnormal κ/λ ratio, often markedly elevated free light chains. |
| Complete blood count | Anaemia, leukopenia, thrombocytopenia | Normocytic anaemia, possible cytopenias. |
| Serum calcium, creatinine, eGFR, albumin, β2‑microglobulin | CRAB features, disease burden | Hypercalcaemia, renal impairment, low albumin, elevated β2‑microglobulin. |
| 24‑hour urine protein electrophoresis | Detects Bence‑Jones protein (light chains) | Presence of monoclonal light chains in urine. |
| Skeletal survey (X‑ray) or low‑dose whole‑body CT | Detects osteolytic lesions | Multiple “punched‑out” lesions, especially skull, spine, ribs. |
| Bone marrow aspirate/biopsy | Clonal plasma‑cell percentage, cytogenetics | ≥10 % clonal plasma cells; may show del(13q), t(4;14), etc. |
| MRI of spine/pelvis (if neurological symptoms) | Evaluates marrow infiltration, plasmacytomas, cord compression | Focal or diffuse marrow replacement; soft‑tissue masses. |
| PET‑CT (optional) | Staging, detection of extramedullary disease | FDG‑avid lesions corresponding to plasmacytomas. |
Diagnosis and severity
Diagnostic criteria (adapted to our setting)
- Clonal bone‑marrow plasma cells ≥10 % or biopsy‑proven plasmacytoma, plus at least one CRAB feature (hyperCalcaemia, Renal insufficiency, Anemia, Bone lesions) or any myeloma‑defining event (≥60 % plasma cells, involved/uninvolved free light‑chain ratio ≥100, >1 focal lesion on MRI).
- Presence of a monoclonal protein in serum and/or urine supports the diagnosis but is not mandatory if marrow criteria are met.
Staging / severity assessment
| Stage | Criteria (simplified) | Clinical implication |
|---|---|---|
| Stage I | β2‑microglobulin <3.5 mg/L and albumin ≥35 g/L | Low tumour burden; better prognosis; may start with oral agents. |
| Stage II | Neither stage I nor III (intermediate values) | Intermediate risk; combination therapy usually required. |
| Stage III | β2‑microglobulin ≥5.5 mg/L or high‑risk cytogenetics (del(17p), t(4;14), t(14;16)) | High tumour burden; aggressive treatment, consider transplant if eligible. |
Renal function (creatinine, eGFR) and performance status (ECOG) further guide urgency of therapy and need for supportive measures (hydration, bisphosphonates, infection prophylaxis).
The above provides a concise, clinically oriented roadmap for Year 4 MBChB students rotating through internal medicine in Kenya, integrating local epidemiological considerations with the universal principles of multiple myeloma care.
Management
| Phase | What to do | Rationale / Safety notes |
|---|---|---|
| Immediate stabilisation | • Give IV fluids (isotonic) to correct dehydration and improve renal perfusion. <br>• Start bisphosphonate infusion (e.g., zoledronic acid or pamidronate) if creatinine ≤ 2 mg/dL; avoid if severe renal failure. <br>• Treat hypercalcaemia with calcitonin and loop diuretic after adequate hydration; monitor electrolytes closely. <br>• Transfuse packed red cells if Hb < 8 g/dL or symptomatic anaemia. | Prevent acute kidney injury, control calcium, maintain oxygen‑carrying capacity. |
| Definitive therapy | Induction (for transplant‑eligible): proteasome inhibitor + immunomodulatory drug + dexamethasone (e.g., bortezomib‑lenalidomide‑dexamethasone). <br>Induction (non‑eligible): proteasome inhibitor + dexamethasone or IMiD + dexamethasone. <br>Stem‑cell transplant: high‑dose melphalan followed by autologous HSCT after 3–4 cycles of induction (if age < 70 and fit). <br>Consolidation/maintenance: lenalidomide or bortezomib based, continued until progression or unacceptable toxicity. | Proteasome inhibition reduces plasma‑cell proliferation; IMiDs enhance immune clearance; steroids provide rapid tumour reduction. Transplant offers deepest remission in eligible patients. |
| Supportive care | • Bisphosphonates every 4 weeks for at least 2 years; switch to denosumab if renal function declines. <br>• Antiviral prophylaxis (e.g., acyclovir) when on proteasome inhibitors. <br>• Pneumocystis prophylaxis (trimethoprim‑sulfamethoxazole) with prolonged steroids. <br>• Vaccinations: pneumococcal, influenza, hepatitis B (if not immune). <br>• Analgesia for bone pain; consider radiotherapy for solitary painful lesions. | Prevent skeletal‑related events, opportunistic infections, and steroid‑related complications. |
| Monitoring | • CBC, calcium, creatinine, LDH every 2–4 weeks during induction. <br>• Serum free light‑chain ratio and M‑protein quantification each cycle. <br>• Skeletal survey or low‑dose whole‑body CT annually or if new pain. <br>• Cardiac & pulmonary assessment before transplant. | Detect early toxicity, assess response (≥ 90 % M‑protein reduction = very good partial response). |
| Contra‑indications / safety | • Bisphosphonates: avoid if CrCl < 30 mL/min without dose adjustment. <br>• Proteasome inhibitors: caution in severe neuropathy or hepatic impairment. <br>• IMiDs: avoid in pregnancy; screen for thrombo‑embolism and give prophylactic anticoagulation if risk high. | Ensure organ function is adequate before each drug class; stop or adjust if toxicity emerges. |
Complications and prognosis
| Complication | Typical presentation | Management principle |
|---|---|---|
| Renal failure (myeloma kidney) | Rising creatinine, oliguria, proteinuria, Bence‑Jones protein casts | Aggressive hydration, avoid nephrotoxins, bisphosphonate dose‑adjust, consider dialysis if refractory |
| Hypercalcaemia | Polyuria, constipation, neuro‑cognitive changes | Hydration, calcitonin, bisphosphonates, monitor cardiac rhythm |
| Pathologic fractures / spinal cord compression | Focal bone pain, neurologic deficit | Orthopaedic fixation or radiotherapy, continue systemic therapy, immobilise |
| Infections (esp. bacterial, viral, fungal) | Fever, neutropenia, opportunistic lesions | Prompt cultures, empiric broad‑spectrum antibiotics, antiviral prophylaxis, consider growth‑factor support |
| Anemia | Fatigue, dyspnoea, pallor | Transfusion, erythropoiesis‑stimulating agents if refractory and iron stores adequate |
| Peripheral neuropathy (from bortezomib or thalidomide) | Tingling, numbness, glove‑stock distribution | Dose‑reduce or switch agent, gabapentin/pregabalin for symptom control |
| Secondary primary malignancies (especially with long‑term IMiDs) | New lesions, unexplained cytopenias | Vigilant surveillance, modify therapy if high risk |
Prognosis – Median overall survival has improved to > 5 years in high‑income settings with modern regimens; in Kenya, outcomes depend on early diagnosis, access to transplant and supportive drugs, and control of co‑morbid infections (HIV, TB). High‑risk cytogenetics (t(4;14), del17p) still confer poorer survival.
High‑yield exam points
- Look‑alike conditions: metastatic bone disease, chronic lymphocytic leukaemia, Waldenström macroglobulinaemia, osteomyelitis.
- Commonest wrong first step: ordering a bone scan before a skeletal survey; the latter is the standard initial imaging for lytic lesions.
- Bedside examiner question: “Explain why the patient’s serum calcium is high despite normal PTH.” (Answer: osteolysis releases calcium; PTH is suppressed.)
- Key bedside sign: “Rouleaux formation” on peripheral smear – stacks of RBCs due to high paraprotein.
- Important safety check: before giving bisphosphonates, always verify renal function; contraindicated if CrCl < 30 mL/min.
- Treatment hierarchy: Stabilise calcium/renal function → start induction therapy → assess transplant eligibility → consider maintenance.
Clinical case
Case: A 58‑year‑old Kenyan man presents with 3 weeks of worsening low‑back pain, fatigue, and nocturnal sweating. He is HIV‑positive on ART, CD4 = 420 cells/µL. Examination reveals pallor, mild peripheral oedema, and a tender lumbar spine. Labs: Hb 9 g/dL, calcium 12.5 mg/dL, creatinine 1.8 mg/dL, β2‑microglobulin elevated, serum protein electrophoresis shows an M‑spike in the γ region, urine immunofixation positive for κ light chains.
Questions
- What is the most urgent management step?
Answer: Initiate aggressive IV hydration and give a bisphosphonate infusion to treat hypercalcaemia and protect renal function.
- Which induction regimen is appropriate for this patient, considering his HIV status?
Answer: A proteasome inhibitor (bortezomib) combined with dexamethasone; add an IMiD (lenalidomide) only after confirming no severe drug‑drug interaction with his ART.
- What finding on imaging would confirm a myeloma‑related skeletal complication?
Answer: Multiple punched‑out lytic lesions on a plain skeletal survey or low‑dose whole‑body CT, especially involving the lumbar vertebrae.
Practice questions
Question 1
A 62‑year‑old woman with known multiple myeloma presents with sudden onset of severe neck pain and weakness of the upper limbs. MRI shows a compressive lesion at C5‑C6. What is the next best step?
A. Start high‑dose steroids and arrange urgent radiotherapy
B. Immediate surgical decompression and stabilisation
C. Increase bisphosphonate frequency
D. Observe and repeat MRI in 2 weeks
Answer: B. Immediate surgical decompression and stabilisation.
Explanation: Spinal cord compression is a neurosurgical emergency; surgery relieves pressure and prevents permanent deficit.
Question 2
A patient on bortezomib develops grade 2 peripheral neuropathy. Which action is most appropriate?
A. Continue full dose, add gabapentin
B. Reduce bortezomib dose or switch to subcutaneous route
C. Stop all therapy and start steroids only
D. Add high‑dose vitamin B12
Answer: B. Reduce bortezomib dose or switch to subcutaneous route.
Explanation: Dose modification is recommended for neuropathy; symptomatic treatment alone is insufficient.
Question 3
Which laboratory result helps differentiate multiple myeloma from Waldenström macroglobulinaemia?
A. Elevated IgM paraprotein
B. Presence of Bence‑Jones protein in urine
C. Serum free light‑chain κ/λ ratio > 100
D. Hypercalcaemia
Answer: A. Elevated IgM paraprotein.
Explanation: Waldenström is characterised by IgM monoclonal protein, whereas myeloma usually has IgG, IgA or light‑chain only.
Question 4
A 55‑year‑old man with newly diagnosed myeloma has CrCl = 25 mL/min. Which bone‑protective agent is safest?
A. Zoledronic acid
B. Pamidronate
C. Denosumab
D. No therapy until renal function improves
Answer: C. Denosumab.
Explanation: Denosumab is not cleared renally and is preferred when renal function is severely impaired.
Question 5
During induction, a patient develops a fever, neutropenia (ANC < 500) and cough. What is the most appropriate immediate management?
A. Start oral amoxicillin‑clavulanate
B. Admit, start broad‑spectrum IV antibiotics, and obtain cultures
C. Give prophylactic fluconazole only
D. Hold chemotherapy and observe
Answer: B. Admit, start broad‑spectrum IV antibiotics, and obtain cultures.
Explanation: Febrile neutropenia is a medical emergency; prompt IV antibiotics reduce mortality.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.