Multiple myeloma

- represents a malignant proliferation of plasma cells derived from a single clone
- incidence increases with age, median age at diagnosis is 70 years
- males are more commonly affected than females
- classic triad of myeloma is marrow plasmacytosis (>10%), lytic bone lesions and serum and/or urine M component

Clinical manifestations
- bone pain is the most common symptom in myeloma (70%), which usually involves the back and ribs. The pain of myeloma is precipitated by movement, unlike pain of metastatic carcinoma which usually worse at night. Osteoclastic activity is mediated by osteoclast activating factors made by myeloma cells
- susceptibility to bacterial infections (usually pneumonias and pyelonephritis) caused by hypogammaglobulinaemia. 
- renal failure (most commonly caused by hypercalcemia. Other causes are glomerular deposits of amyloid, hyperuricemia, tubular damage by light chains, frequent use of NSAIDs, infiltration of kidney by myeloma cells, use of iodinated contrast dye for imaging). Earliest manifestation of tubular damage is adult Fanconi syndrome
- normochromic normocytic anaemia caused by replacement of normal marrow by expanding tumor cells, inhibition of hematopoiesis by factors made by tumor and reduced production of erythropoeitin by kidney
- hyperviscosity may developed depending on physical properties of M component (most common with IgM, IgG3 and IgA paraprotein)

Diagnosis
- important differential diagnosis are MGUS (serum M protein <30g/L and bone marrow clonal plasma cells <10%) and asymptomatic/smoldering myeloma
- Investigations
i) Chest and bone radiographs - lytic lesions or diffuse osteopenia
ii) Full blood picture- anemia and Rouleux formation
iii) ESR - elevated
iv) serum calcium, urea nitrogen, creatinine and uric acid levels may be elevated
v) serum and urine protein electrophoresis - characteristic M spikes
vi) 24-h urine specimen to quantiate Bence Jones protein excretion
vii) serum B2-microglobulin (single most powerful predictor of survival)






Treatment
- 10% of patients with indolent/smoldering myeloma only require antitumor therapy when the disease becomes symptomatic
- supportive care directed at the anticipated complications (bisphosphonates, steroid, hydration for hypercalcemia; plasmapheresis for acute renal failure and hyperviscosity syndrome)
- Bortezomib (proteasome inhibitor) and lenalidomide combined with dexamethasone obtained high response rate (>80%) without compromising stem cell collection for transplantation
- For patients not transplant candidate, therapy consisting of intermittent pulses of an alkylating agent, melphalan with prednisolone
- radiotherapy is effective for bony lesions
- Median survival is 7-8 years. Major causes of death are progressive myeloma, renal failure, sepsis, or therapy-related myelodysplasia