What are the best options for managing pain associated with multiple myeloma (MM) lytic bone lesions?

Management of Pain Associated with Multiple Myeloma Lytic Bone Lesions

The management of pain from multiple myeloma (MM) lytic bone lesions requires a multimodal approach including bisphosphonates, anti-myeloma therapy, radiotherapy, interventional procedures, and appropriate analgesics, with bisphosphonates being the cornerstone of treatment alongside anti-myeloma therapy. 1

First-Line Approaches

Bisphosphonates and Anti-Myeloma Therapy

• Zoledronic acid (4 mg IV) or pamidronate are recommended for all MM patients with bone disease and adequate renal function, administered monthly 1, 2
• Bisphosphonates should be given continuously, though it's unclear if patients achieving very good partial response benefit from continuous use 1
• Dose adjustments are required for patients with renal impairment:
  • For CrCl 30-60 mL/min: reduced doses of zoledronic acid with no change to infusion time, or pamidronate via 4-hour infusion 1
  • For CrCl <30 mL/min: both pamidronate and zoledronic acid should be avoided 1
• Renal function should be monitored before each infusion, with treatment discontinued if renal function deteriorates 1, 2

Radiotherapy

• Indicated for symptomatic spinal cord compression, extremely painful lytic lesions, and prevention of pathological fractures 1
• For painful osteolytic lesions, a dose of 3000 cGy in 10-15 fractions is typically effective 1
• Note that radiotherapy may delay systemic anti-myeloma therapies that include radiosensitizing drugs 1

Interventional Procedures

Balloon Kyphoplasty and Vertebroplasty

• Balloon kyphoplasty is the treatment of choice for painful vertebral compression fractures, with approximately 80% of patients experiencing pain relief 1
• These techniques are particularly valuable for patients with pain unresponsive to conventional analgesics 1
• Balloon kyphoplasty is associated with reduced rates of cement leakage compared to vertebroplasty 1

Surgery

• Indicated for:
  • Fixation of pathological fractures of long bones
  • Prevention and restoration of axial skeleton in cases of unstable spinal fractures
  • Spinal cord compression with bone fragments within the spinal route 1

Pharmacological Pain Management

For Acute Severe Pain

• Subcutaneous opioids (oxycodone or morphine injection) are recommended for rapid relief of symptoms 1
• All patients on opioids should also receive laxatives to prevent constipation 1

For Chronic Pain

• Calcium channel blockers (gabapentin or pregabalin) 1
• Sodium channel blockers (lidocaine, oxcarbazepine) 1
• Serotonin-norepinephrine reuptake inhibitors (duloxetine or amitriptyline) 1

Nerve Blocks

• Neurolytic blocks using chemicals, heat, or freezing may produce long-lasting pain relief for weeks, months, or indefinitely 1

Special Considerations

Monitoring and Follow-up

• Regular assessment of pain control and medication side effects is essential 3
• Renal function must be carefully monitored in all patients receiving bisphosphonates 2, 4
• Before bisphosphonate administration, patients should have a thorough dental examination to prevent osteonecrosis of the jaw 1

Potential Complications

• Osteonecrosis of the jaw is a rare but serious complication of bisphosphonate therapy 1
• Renal toxicity can occur with bisphosphonates, particularly with rapid infusion rates 2, 4
• Hypocalcemia may occur, especially in patients on dialysis 1

Emerging Therapies

• Denosumab is being investigated for myeloma patients and can currently be used only in rare cases of hypercalcemia resistant to bisphosphonates 1
• Percutaneous trochanteroplasty may be beneficial for pain relief in patients with trochanteric lytic lesions 5

Comprehensive Approach

• Pain management in MM requires a multidisciplinary approach involving hematologists, pain specialists, radiation oncologists, and orthopedic surgeons 6
• The goal is not only to reduce pain but also to prevent skeletal-related events and improve quality of life 7, 8