Can an elective surgery be safely performed on a patient with multiple myeloma receiving immunotherapy, and what pre‑operative precautions are required?

Elective Surgery in Multiple Myeloma Patients on Immunotherapy

Elective surgery can be safely performed in multiple myeloma patients receiving immunotherapy, but requires careful pre-operative risk assessment, multidisciplinary coordination, and specific precautions related to both the underlying disease and immunotherapy-related complications.

Key Pre-operative Considerations

Disease-Specific Assessment

Before proceeding with elective surgery, evaluate:

• Bone disease burden: Obtain whole-body low-dose CT scan (superior to skeletal survey) to assess for occult lytic lesions that could compromise surgical sites or positioning 1, 2
• Renal function: Critical given high risk of acute renal failure perioperatively (25.97% in surgical series) 3
• Hematologic parameters: Assess for cytopenias, hyperviscosity, and coagulation abnormalities
• Calcium levels: Screen for hypercalcemia which complicates 10.39% of perioperative cases 3

Immunotherapy-Specific Precautions

For patients on monoclonal antibodies (daratumumab, elotuzumab, isatuximab):

• These agents can interfere with serological testing and cause false-positive indirect Coombs tests 1
• Coordinate with blood bank pre-operatively for type and screen
• Consider timing surgery to avoid infusion-related reactions (most common with first 4 cycles) 4

For patients on immunomodulatory drugs (lenalidomide, pomalidomide):

• Thromboembolism prophylaxis is mandatory: Use therapeutic anticoagulation for high-risk patients; full-dose aspirin minimum for lower-risk 1
• Patients with multiple myeloma on immunotherapy have 2.97-fold increased risk of thromboembolic events perioperatively 5

For patients on proteasome inhibitors (bortezomib, carfilzomib, ixazomib):

• Assess for pre-existing peripheral neuropathy that may affect positioning and post-operative mobility 1
• Ensure herpes zoster prophylaxis is in place 1

Perioperative Risk Profile

Multiple myeloma patients undergoing elective surgery face significantly elevated risks 5:

• Surgical site infection: 2.82-fold increased risk (OR: 2.82,95% CI: 1.59-5.01)
• Thromboembolic events: 2.97-fold increased risk (OR: 2.97,95% CI: 2.32-3.81)
• Acute renal failure: 1.93-fold increased risk (OR: 1.93,95% CI: 1.59-2.37)
• Blood transfusion requirement: 2.14-fold increased risk (28.57% in one series) 3, 5
• Prolonged hospital stay: 2.04-fold increased risk 5

The overall complication rate following surgery in multiple myeloma is 74%, though only 20.78% are surgical complications—the majority are medical 3.

Timing of Surgery

Optimal timing relative to immunotherapy:

• Avoid surgery during active infusion-related reaction risk periods (first 4 cycles of monoclonal antibodies) 4
• For patients on continuous lenalidomide or pomalidomide, maintain anticoagulation throughout perioperative period 6, 7
• Consider delaying truly elective procedures if patient is achieving deep response to current therapy, as surgical indication itself portends worse prognosis 8

Mandatory Pre-operative Interventions

1. Thromboprophylaxis protocol:

   • Initiate pharmacologic prophylaxis pre-operatively with LMWH or UFH 6, 7
   • Continue for minimum 7-10 days post-operatively
   • Consider extended prophylaxis (up to 4 weeks) for major procedures 7

2. Infection prophylaxis:

   • Ensure herpes zoster prophylaxis for patients on proteasome inhibitors 1
   • Consider pneumococcal vaccination if not current 1
   • Maintain high index of suspicion given 24.68% infection rate 3

3. Renal protection:

   • Optimize hydration status
   • Avoid nephrotoxic agents
   • Monitor closely given 25.97% acute renal failure rate 3

4. Bisphosphonate considerations:

   • Dental examination mandatory before starting bisphosphonates 1
   • Monitor for osteonecrosis of jaw risk perioperatively 1

Multidisciplinary Coordination

Essential team involvement 3, 9:

• Hematology/oncology for immunotherapy management
• Anesthesiology for risk stratification
• Orthopedic surgery if bone lesions present
• Internal medicine for medical comorbidity optimization

Post-operative Monitoring

• Intensive surveillance for infection (25% develop post-operative infection) 3
• Daily renal function monitoring for first 72 hours
• Thromboembolism vigilance with low threshold for imaging
• Calcium monitoring for hypercalcemia (10.39% incidence) 3

Critical Caveats

Do not proceed with elective surgery if:

• Active, uncontrolled infection present
• Severe cytopenias without transfusion support available
• Uncontrolled hypercalcemia
• Symptomatic hyperviscosity requiring plasmapheresis 1
• Recent immune-related adverse events from immunotherapy requiring high-dose steroids 4

Important prognostic consideration: The need for surgical intervention in multiple myeloma itself indicates worse prognosis, with median survival of 42 months in those requiring but not receiving surgery versus 62 months in those without surgical indication 8. However, patients who undergo indicated surgery have better outcomes (58 months median survival) than those who cannot be operated on despite indication 8.

The decision to proceed should weigh the functional benefit and quality of life improvement from surgery against the substantial perioperative risks, with realistic discussion of the 32.9-month median overall survival post-operatively 3.