Multiple myeloma (MM) is a clonal plasma cell neoplasm in the bone marrow producing a monoclonal immunoglobulin (M-protein). Median age at diagnosis: 69 years, more common in African Americans (2ร). The disease spectrum: MGUS โ smoldering myeloma โ active myeloma. Active myeloma requires CRAB criteria (end-organ damage): C alcium elevated (> 11) ยท R enal insufficiency (Cr > 2) ยท A nemia (Hgb < 10) ยท B one lesions (lytic on skeletal survey or PET/CT). SLiM criteria added in 2014: S ixty percent bone marrow plasma cells ยท Li ght chain ratio โฅ 100 ยท M RI with > 1 focal lesion โฅ 5mm -these define myeloma even without CRAB. IMWG, 2014
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Bortezomib | 1.3 mg/mยฒ SQ weekly | SQ | Proteasome inhibitor. Peripheral neuropathy (dose-limiting). VZV reactivation โ acyclovir prophylaxis. SWOG S0777, 2017 |
| Lenalidomide | 25 mg PO days 1-21/28 | PO | IMiD. VTE risk โ thromboprophylaxis. Teratogenic. Dose-reduce for CrCl < 30. Maintenance post-ASCT: 10-15 mg. |
| Daratumumab | 16 mg/kg IV weekly โ q2w โ q4w | IV/SQ | Anti-CD38 mAb. Infusion reactions (pre-medicate). Interferes with blood bank crossmatch (anti-CD38 on reagent RBCs). MAIA, 2019 |
| Dexamethasone | 40 mg weekly (20 mg if > 75y) | PO | Backbone of all myeloma regimens. Hyperglycemia, insomnia, mood changes, infection risk. |
| Zoledronic acid | 4 mg IV over 15 min q4w | IV | Bone-modifying agent. Reduces SREs. Dental exam before starting (ONJ risk). Dose-adjust for CrCl. MRC Myeloma IX, 2012 |
| Carfilzomib | 20-56 mg/mยฒ IV | IV | 2nd-gen proteasome inhibitor for relapsed MM. Cardiac toxicity (HF, HTN) -check echo baseline. Less neuropathy than bortezomib. |
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Bortezomib | 1.3 mg/mยฒ SQ weekly | SQ | Proteasome inhibitor. Peripheral neuropathy (dose-limiting). VZV reactivation โ acyclovir prophylaxis. SWOG S0777, 2017 |
| Lenalidomide | 25 mg PO days 1-21/28 | PO | IMiD. VTE risk โ thromboprophylaxis. Teratogenic. Dose-reduce for CrCl < 30. Maintenance post-ASCT: 10-15 mg. |
| Daratumumab | 16 mg/kg IV weekly โ q2w โ q4w | IV/SQ | Anti-CD38 mAb. Infusion reactions (pre-medicate). Interferes with blood bank crossmatch (anti-CD38 on reagent RBCs). MAIA, 2019 |
| Dexamethasone | 40 mg weekly (20 mg if > 75y) | PO | Backbone of all myeloma regimens. Hyperglycemia, insomnia, mood changes, infection risk. |
| Zoledronic acid | 4 mg IV over 15 min q4w | IV | Bone-modifying agent. Reduces SREs. Dental exam before starting (ONJ risk). Dose-adjust for CrCl. MRC Myeloma IX, 2012 |
| Carfilzomib | 20-56 mg/mยฒ IV | IV | 2nd-gen proteasome inhibitor for relapsed MM. Cardiac toxicity (HF, HTN) -check echo baseline. Less neuropathy than bortezomib. |
Patient: 68M with fatigue, bone pain, and foamy urine ร 2 months. Hgb 8.2, Ca 13.4, Cr 3.8 (baseline 1.0), total protein 10.8. SPEP: IgG kappa M-spike 5.1 g/dL. sFLC kappa 1240, ratio 98. BMBx: 72% clonal plasma cells.
Key findings: Active myeloma: CRAB criteria met (Ca 13.4, Renal Cr 3.8, Anemia Hgb 8.2) + SLiM (72% plasma cells). Myeloma kidney (cast nephropathy), light chains forming obstructive casts in distal tubules.
Management:
Teaching point: Myeloma kidney is driven by free light chains, not M-protein. Rapid light chain reduction with bortezomib-based therapy is key to renal recovery. ~50% of patients with myeloma kidney recover renal function if treated promptly.
Patient: 58F with back pain and pathologic L2 compression fracture. Hgb 9.8, Ca 10.8, Cr 1.1. SPEP: IgA lambda M-spike 3.2 g/dL. BMBx: 45% plasma cells. PET/CT: multiple lytic lesions. FISH: standard risk [t(11;14)].
Key findings: Standard-risk myeloma. Fit, age < 65, transplant-eligible. Bone disease with pathologic fracture. Standard risk t(11;14) has favorable prognosis.
Management:
Teaching point: Lenalidomide maintenance after ASCT is standard of care, it roughly doubles PFS. For t(11;14) specifically, venetoclax-based combinations are emerging as highly effective (BCL-2 overexpression).
Patient: 62M found to have M-spike 2.8 g/dL on routine labs. Asymptomatic. Hgb 13.2, Ca 9.8, Cr 0.9. sFLC ratio 18. BMBx: 22% plasma cells. No lytic lesions on PET/CT. No SLiM criteria.
Key findings: Smoldering myeloma: โฅ 10% plasma cells + M-protein โฅ 3 g/dL, but NO CRAB or SLiM criteria. Risk of progression ~10%/year for first 5 years. High-risk features: sFLC ratio > 20, M-spike > 2, BMBx > 20%.
Management:
Teaching point: Treating smoldering myeloma is NOT standard of care outside clinical trials. The CRAB and SLiM criteria define the line between observation and treatment. However, high-risk smoldering patients may benefit from early intervention, encourage trial enrollment.
Mr. Wallace is a 71-year-old man presenting with progressive low back pain ร 3 months, fatigue, and 15 lb weight loss. Found to have: Hgb 8.4, Ca 12.8, Cr 2.6, total protein 11.2. SPEP: IgG kappa M-spike 4.2 g/dL. sFLC: kappa 890, lambda 12, ratio 74. Skeletal survey: multiple lytic lesions in spine, pelvis, skull. BMBx: 65% clonal plasma cells, FISH: standard risk.