Multiple Myeloma and Plasma Cell Disorders

Multiple Myeloma: The Basics - Plasma Cell Proliferation

• Malignant neoplastic proliferation of monoclonal plasma cells, primarily in bone marrow.
• Derived from post-germinal center B-cells.
• Secretes monoclonal immunoglobulin (M-protein/paraprotein).
  • Most common: IgG (~55%), IgA (~20%).
  • Light chains only (Bence Jones protein in urine) in ~20% of cases.
• Pathogenesis involves complex genetic abnormalities and bone marrow microenvironment interactions.

⭐ Rouleaux formation (RBCs stacked like coins) on peripheral smear is a characteristic finding due to ↑ serum proteins (M-protein).

Clinical & Lab Clues - CRAB's Sinister Signs

📌 CRAB Criteria (myeloma-defining organ damage):

• Calcium: Serum Ca > 11 mg/dL or > 1 mg/dL above ULN.
• Renal: S.Cr > 2 mg/dL or CrCl < 40 mL/min.
• Anemia: Hb < 10 g/dL or > 2 g/dL below normal.
• Bone: ≥1 lytic lesions on imaging (X-ray, CT, PET-CT).

Other symptoms: Most common: bone pain (back/ribs); also pathological fractures, fatigue, recurrent infections. Initial lab clues: ↑ ESR, ↑ total protein (globulin gap). Diagnostic pointers:

• SPEP: M-protein (IgG > IgA)
• UPEP: Bence Jones proteinuria
• SFLC assay: Abnormal κ/λ ratio

⭐ Hypercalcemia can cause confusion, constipation, and cardiac arrhythmias; it's a common oncologic emergency in MM patients.

Diagnosis & Staging - Nailing the Diagnosis

• IMWG Criteria for MM:
  • Clonal BM plasma cells ≥10% / Plasmacytoma.
  • AND ≥1 MDE (Myeloma Defining Event):
    • 📌 CRAB: Ca >11mg/dL, Renal (CrCl<40ml/min), Anemia (Hb<10g/dL), Bone (≥1 lytic lesion).
    • SLiM: Sixty (≥60%) BM plasma cells, Light chain (FLC) ratio ≥100, MRI >1 focal lesion (≥5mm).
• SMM (Smoldering Multiple Myeloma): M-protein (e.g., Serum IgG ≥3g/dL) AND/OR BM plasma cells 10-59%, with NO MDEs.

⭐ Rouleaux formation on peripheral smear: classic (non-specific) finding in MM due to ↑ paraproteins.

Staging (ISS & R-ISS):

MM Management - Battling the Burden

• Goal: Prolong survival, control disease, improve quality of life (QoL).
• Treatment Approach: Risk-stratified; based on Autologous Stem Cell Transplant (ASCT) eligibility.

• Key Drug Classes & Examples:
  • Proteasome Inhibitors (PIs): Bortezomib (📌 watch for neuropathy), Carfilzomib.
  • Immunomodulatory Drugs (IMiDs): Lenalidomide (📌 for maintenance), Pomalidomide.
  • Monoclonal Antibodies (mAbs): Daratumumab (anti-CD38).
  • Alkylating agents: Melphalan (ASCT), Cyclophosphamide.
• Supportive Care Essentials:
  • Bisphosphonates (e.g., Zoledronic acid) for bone protection.
  • Manage: Anemia (ESA/transfusion), Infections (prophylaxis), Renal failure, Hypercalcemia.
  • VTE prophylaxis (especially with IMiDs).

⭐ Bortezomib, a proteasome inhibitor, is a cornerstone of MM therapy; peripheral neuropathy is a notable side effect.

Other Plasma Cell Players - MGUS & Waldenström's Glimpse

High‑Yield Points - ⚡ Biggest Takeaways

• Multiple Myeloma: Plasma cell dyscrasia with CRAB criteria (HyperCalcemia, Renal failure, Anemia, Bone lesions).
• Hallmark: Monoclonal M-protein (IgG > IgA) in serum/urine; Bence Jones proteinuria (light chains).
• Diagnosis: >10% clonal plasma cells in bone marrow; peripheral smear shows Rouleaux formation.
• MGUS (Monoclonal Gammopathy of Undetermined Significance): Precursor; M-protein <3 g/dL, <10% marrow plasma cells, no CRAB.
• Waldenström's Macroglobulinemia: IgM hypersecretion, hyperviscosity, lymphadenopathy, no lytic bone lesions.
• Key complications: Infections, renal failure, amyloidosis, pathological fractures.