What is the role of therapeutic plasma exchange (PEX) and other treatments in managing Thrombotic Thrombocytopenic Purpura (TTP) in patients with Multiple Myeloma?

Role of Therapeutic Plasma Exchange in TTP and Multiple Myeloma

Plasma exchange is recommended in multiple myeloma patients with rapidly progressing renal failure and in those with symptomatic hyperviscosity syndrome, but is not indicated for primary treatment of TTP in multiple myeloma patients unless there are specific complications requiring it. 1

Therapeutic Plasma Exchange in Multiple Myeloma Complications

Renal Failure

• Plasma exchange is effective in removing monoclonal light chains responsible for renal failure and may restore normal renal function in more than half of patients 1
• Most beneficial in patients with rapidly progressive renal failure secondary to multiple myeloma 1
• Should be performed in combination with corticosteroids 1
• Protocol:
  • Replace approximately two-thirds of the patient's plasma volume with 5% human albumin solution or an equal mixture of albumin and 0.9% normal saline 2
  • Perform daily for 3-5 days until hyperviscosity is corrected 2
  • Must be combined with prompt initiation of effective chemotherapy 1

Hyperviscosity Syndrome

• Occurs in less than 2% of multiple myeloma patients at diagnosis 1
• Clinical manifestations include mucosal hemorrhage, visual abnormalities, neurologic symptoms, and cardiac features 1
• Usually occurs when monoclonal protein concentration exceeds 40 g/L 2
• Treatment protocol:
  • Automated plasma exchange with 5% human albumin solution 1
  • Dramatic response often seen after first plasma exchange session 1
  • Repeat at scheduled intervals, generally daily for 3-5 days 1
  • Must be followed by prompt initiation of chemotherapy to prevent recurrence of symptoms within 2-3 weeks 1

TTP in Multiple Myeloma

TTP (Thrombotic Thrombocytopenic Purpura) is not a common complication of multiple myeloma itself. When TTP occurs in patients with multiple myeloma, it should be treated according to standard TTP protocols:

• First-line treatment is plasma exchange combined with immunosuppressive therapy 3
• Caplacizumab (CABLIVI) is indicated for adult patients with acquired TTP, in combination with plasma exchange and immunosuppressive therapy 3
• Treatment protocol for TTP:
  • Single 11 mg caplacizumab bolus IV injection prior to first plasma exchange 3
  • Daily subcutaneous injection of 11 mg caplacizumab after completion of plasma exchange 3
  • Continue for duration of daily plasma exchange period and for 30 days thereafter 3

Effectiveness and Outcomes

• Plasma exchange in multiple myeloma with renal failure has shown improvement in overall survival, particularly in patients whose renal function recovered 1
• Complete response rates of 85.3% have been reported in TTP patients treated with plasma exchange 4
• Recent data shows that among multiple myeloma patients with cast nephropathy treated with TPE, 48.75% achieved renal response 5
• Achievement of renal response is crucial for prolonged overall survival in multiple myeloma patients 5

Potential Complications and Management

• Adverse reactions occur in approximately 9.7% of plasma exchange procedures 6
• Most common complications:
  • Hypocalcemia (can be prevented with prophylactic calcium administration) 6
  • Hypovolemia 6
  • Anaphylactoid reactions (more common with fresh-frozen plasma than albumin) 6
• Serious complications are rare:
  • Cardiovascular events (0.2%) 6
  • Respiratory events (0.2%) 6
  • Severe anaphylactoid reactions (0.25%) 6
  • Mortality rate is approximately 0.05% 6

Practical Considerations

• For refractory cases of TTP, twice-daily plasma exchange may be beneficial 7
• Vascular access is critical for successful plasma exchange, with peripheral venous access suitable for short-term treatments 2
• Medication dosing may need adjustment before or after procedures 2
• The use of plasma exchange in multiple myeloma has increased substantially in recent years, with associated increases in cost 8

Important Caveats

• Plasma exchange should be initiated promptly in rapidly progressive renal failure or symptomatic hyperviscosity
• Must always be combined with definitive therapy (chemotherapy) for the underlying multiple myeloma
• For multiple myeloma patients with renal failure, bortezomib-based regimens are recommended as first-line therapy 1
• Daratumumab-based therapies show promise for improving outcomes in newly diagnosed multiple myeloma patients with cast nephropathy 5

Remember that plasma exchange is a supportive measure, not a definitive treatment for multiple myeloma. It should be used as part of a comprehensive treatment approach that includes appropriate chemotherapy regimens targeting the underlying plasma cell disorder.