What is the role of plasmapheresis (plasma exchange) in the treatment of a patient with multiple myeloma?

Role of Plasmapheresis in Multiple Myeloma

Plasmapheresis should be used immediately for symptomatic hyperviscosity syndrome in multiple myeloma patients, but its role for acute kidney injury from cast nephropathy remains controversial with weak evidence, warranting a Category 2B recommendation only when combined with aggressive bortezomib-based chemotherapy in highly selected patients with severe light chain burden. 1

Established Indications for Plasmapheresis

Symptomatic Hyperviscosity Syndrome

• Plasmapheresis is the definitive immediate therapy for symptomatic hyperviscosity and should be initiated urgently. 1
• Continue plasmapheresis sessions until acute symptoms (visual disturbances, bleeding, neurologic symptoms) resolve. 2
• This indication has uniform consensus across all major guidelines and represents a life-threatening emergency requiring rapid intervention. 1

Prevention of IgM Flare with Rituximab

• In patients with high IgM levels (typically >4000 mg/dL), perform preemptive plasmapheresis before rituximab administration to prevent IgM flare. 1, 2
• This is particularly relevant in Waldenström's macroglobulinemia but applies to IgM myeloma cases. 1

Controversial Indication: Acute Kidney Injury from Cast Nephropathy

The Evidence Dilemma

The use of plasmapheresis for myeloma-related acute kidney injury shows conflicting evidence from randomized trials with no clear mortality or renal recovery benefit demonstrated:

• Three randomized trials yielded inconsistent results: one showed benefit (Zucchelli), two showed no significant benefit (Johnson, Clark). 1
• The Clark trial (largest, 97 patients) showed no significant difference in dialysis independence (17.9% vs 8.6%) or mortality (33.3% vs 32.8%) between plasmapheresis and control groups. 1
• NCCN guidelines rate plasmapheresis for renal dysfunction as Category 2B (lowest recommendation level), acknowledging institutional variation in practice. 1

When to Consider Plasmapheresis for Cast Nephropathy

If you choose to use plasmapheresis for acute kidney injury, apply these strict criteria:

• Serum free light chains (sFLC) ≥500 mg/L (preferably >150 mg/dL with urine M-spike >200 mg/day). 1, 2
• Initiate within 1 month of kidney injury onset—early intervention is critical. 1, 2
• Must be combined with rapid-acting bortezomib-based chemotherapy (VCD/VTD/VD) plus daily plasmapheresis. 1
• Target >50% reduction of involved FLC from baseline and involved FLC <50 mg/dL by end of cycle 1. 1
• Perform ≥3 plasmapheresis sessions minimum; studies show higher FLC reduction and longer survival with ≥3 sessions versus 2 sessions. 3

Critical Pitfalls with Plasmapheresis for Renal Failure

• Plasmapheresis alone does not affect plasma cells and cannot stop ongoing light chain production—it must be combined with effective chemotherapy. 4, 5, 6
• Light chains rebound rapidly (within 5-10 hours) after each session due to redistribution from extravascular compartments and continued production. 6
• Some patients show paradoxical increases in sFLC levels (-70% to +40% removal variability) despite plasmapheresis. 6
• Plasmapheresis is ineffective if chemotherapy fails to suppress tumor burden—extracorporeal removal alone cannot overcome high production rates. 2

Practical Algorithm for Decision-Making

Step 1: Identify the Clinical Scenario

• Hyperviscosity symptoms (visual changes, bleeding, confusion)? → Immediate plasmapheresis, no debate. 1
• High IgM before rituximab? → Preemptive plasmapheresis. 1, 2
• Acute kidney injury with suspected cast nephropathy? → Proceed to Step 2.

Step 2: Risk Stratify for Cast Nephropathy

• Involved FLC <150 mg/dL: Consider kidney biopsy; plasmapheresis not indicated. 1
• Involved FLC >150 mg/dL but urine M-spike <200 mg/day or albuminuria >10%: Likely not pure cast nephropathy; plasmapheresis questionable benefit. 1
• Involved FLC >150 mg/dL AND urine M-spike >200 mg/day AND albuminuria <10%: Presumed cast nephropathy—proceed to Step 3. 1

Step 3: Implement Combined Therapy Protocol

• Start daratumumab-based or bortezomib-based chemotherapy (VCD/VTD/VD) immediately. 1
• Add daily plasmapheresis for minimum 5-7 sessions over first 10 days. 1, 3
• Monitor sFLC levels closely; target >50% reduction by end of cycle 1. 1
• Maintain aggressive hydration and avoid NSAIDs/IV contrast. 1

Step 4: Reassess Early

• If sFLC not declining by 50% after 3-4 plasmapheresis sessions, question continuation—chemotherapy may be inadequate. 6, 3
• If renal function not improving despite FLC reduction, plasmapheresis unlikely to provide additional benefit. 4, 6

Key Supportive Measures

• Hydration is mandatory to decrease renal tubular light chain concentration and prevent further cast formation. 1
• Avoid nephrotoxins (NSAIDs, IV contrast) in all patients with renal impairment. 1, 7
• Bortezomib-based regimens can be administered without dose adjustment in severe renal impairment and dialysis, making them ideal for cast nephropathy. 8

Bottom Line on Renal Indication

Given the weak and conflicting evidence, plasmapheresis for cast nephropathy should be reserved for highly selected patients with severe light chain burden (sFLC ≥500 mg/L), early presentation (<1 month), and only when combined with aggressive bortezomib-based chemotherapy. 1 The primary focus must be rapid tumor cytoreduction with effective chemotherapy—plasmapheresis is at best an adjunct that may provide marginal benefit in this narrow context. 4, 2