Multiple Myeloma in the haematology department.pptx
- 2. Introduction Definition: • Multiple Myeloma (MM) is a malignant plasma cell disorder characterized by the clonal proliferation of plasma cells in the bone marrow, leading to the overproduction of monoclonal immunoglobulins (M-protein) or light chains, and associated with end-organ damage. Epidemiology: • Accounts for ~10% of hematologic malignancies. • Median age at diagnosis: 65–70 years. • More common in males and African descent.
- 3. Etiology & Risk Factors: • Age (increased risk >60 years) • Radiation exposure • Chronic antigen stimulation (autoimmune disease) • Pesticides and industrial exposure • Genetic predisposition • Precursor states: • MGUS (Monoclonal Gammopathy of Undetermined Significance) • Smoldering myeloma
- 4. Pathophysiology: • Malignant plasma cells accumulate in the bone marrow and produce a monoclonal immunoglobulin (usually IgG or IgA) or light chains (κ or λ). • Excess light chains (Bence Jones proteins) are filtered by kidneys → renal damage. Plasma cells release cytokines (IL-6, TNF) that: • Stimulate osteoclasts bone resorption and lytic lesions → • Inhibit osteoblasts • Normal immunoglobulin production is suppressed immunodeficiency →
- 5. Clinical Features: • Use the CRAB acronym for end-organ damage: Feature Explanation C – HyperCalcemia From bone destruction; symptoms: fatigue, confusion, constipation R – Renal failure Due to light chains causing cast nephropathy A – Anemia Normocytic normochromic; due to marrow infiltration B – Bone pain Due to lytic lesions, especially in spine, ribs, pelvis
- 6. Other manifestations: • Recurrent infections (due to hypogammaglobulinemia) • Spinal cord compression (from vertebral collapse or plasmacytoma) • Peripheral neuropathy (rare; associated with amyloidosis or POEMS syndrome) • Bleeding tendency (platelet dysfunction)
- 7. Types of Monoclonal Proteins: • IgG (60%) • IgA (20%) • Light-chain only (Bence Jones myeloma) (15%) • Non-secretory myeloma (<2%)
- 8. Diagnostic Criteria (IMWG 2014): Diagnosis requires ≥10% clonal plasma cells in bone marrow or biopsy-proven plasmacytoma, PLUS one of: CRAB Criteria (end-organ damage): • C: Serum calcium >11 mg/dL • R: Serum creatinine >2 mg/dL or eGFR <40 mL/min • A: Hemoglobin <10 g/dL or >2 g/dL below normal • B: One or more lytic bone lesions on imaging Myeloma-defining Events (Biomarkers): • Clonal plasma cells ≥60% in bone marrow • Involved/uninvolved serum free light chain ratio ≥100 • > 1 focal lesion on MRI (>5 mm in size)
- 9. Laboratory Diagnosis: Investigation Findings FBC Normocytic normochromic anemia ± leukopenia/thrombocytopenia Peripheral smear Rouleaux formation (stacked RBCs) Serum protein electrophoresis (SPEP) M-protein spike Urine protein electrophoresis (UPEP) Bence Jones proteins (free light chains) Serum free light chain assay Abnormal κ/λ ratio Bone marrow biopsy ≥10% clonal plasma cells
- 10. Laboratory Diagnosis: Investigation Findings Serum calcium & creatinine Elevated ESR Very high due to increased protein Beta-2 microglobulin Elevated → worse prognosis LDH Elevated in aggressive disease Immunofixation Identifies specific monoclonal immunoglobulin class Flow cytometry CD138+, CD38+, monoclonal light chain restriction
- 11. Peripheral Blood film for MM
- 12. Bone marrow smear for MM
- 13. Staging (Revised International Staging System - R-ISS): Stage Criteria Stage I β2-microglobulin <3.5 mg/L, albumin ≥3.5 g/dL, normal LDH, no high-risk cytogenetics Stage II Not Stage I or III Stage III β2-microglobulin ≥5.5 mg/L with high-risk cytogenetics or elevated LDH High-risk cytogenetics: del(17p), t(4;14), t(14;16)
- 14. Management: 1. Initial Therapy (Induction): Triple-drug regimens: • VRd: Bortezomib (proteasome inhibitor) + Lenalidomide (IMiD) + Dexamethasone • VTD: Bortezomib + Thalidomide + Dexamethasone 2. Autologous Stem Cell Transplant (ASCT): • Offered to eligible patients <70 years with good performance status. • Not curative but prolongs survival and remission.
- 15. Management: 3. Maintenance Therapy: • Lenalidomide post-ASCT prolongs progression-free survival. 4. Relapsed/Refractory Disease: • Re-treatment with different drug classes: • Carfilzomib, Daratumumab, Elotuzumab, Ixazomib Consider clinical trials or second ASCT
- 16. Management: 5. Supportive Treatment: • Bone disease: Bisphosphonates (Zoledronic acid or Pamidronate) • Anemia: Erythropoietin-stimulating agents, transfusions • Infections: Vaccination (pneumococcus, influenza), IVIG if recurrent infections • Renal protection: Hydration, avoid NSAIDs and contrast agents
- 17. Summary Table: Feature Multiple Myeloma Cell type Plasma cells Key marker Monoclonal protein (M-spike) Smear feature Rouleaux formation Bone marrow ≥10% plasma cells Classic signs CRAB (Calcium, Renal, Anemia, Bone lesions) Most common Ig IgG Complications Infections, fractures, renal failure Main drugs Bortezomib, Lenalidomide, Dexamethasone Transplant ASCT if eligible