What is the role of thalidomide in treating multiple myeloma?

Role of Thalidomide in Multiple Myeloma Treatment

Thalidomide is primarily indicated for relapsed/refractory multiple myeloma in combination with dexamethasone and/or chemotherapy, and as maintenance therapy after autologous stem cell transplantation to prolong progression-free survival and overall survival. 1

Treatment Indications for Thalidomide

Relapsed/Refractory Multiple Myeloma

• First-line option for relapsed/refractory multiple myeloma patients 2
• Preferred in combination with dexamethasone and/or chemotherapy rather than as monotherapy 1
• Initial dose of 100-200 mg/day (lower doses may maintain efficacy with better tolerability) 2, 1
• Response rates of approximately 60-70% when used in combination therapy 3, 4

Induction Therapy

• Can be used in combination with dexamethasone as an alternative to the classical VAD regimen before autologous stem cell transplantation 2
• Helps increase complete remission rates before transplantation 2

Maintenance Therapy

• Thalidomide maintenance after autologous stem cell transplantation increases complete remission rates and prolongs progression-free survival and overall survival 2
• Provides benefit in patients who achieve partial remission after transplantation 2

Treatment Algorithms

For Relapsed/Refractory Myeloma:

1. Assess eligibility: Particularly beneficial for patients who have failed initial treatment with melphalan/prednisone or have relapsed after autologous transplant 1
2. Starting dose: 100-200 mg/day orally for 21 days in 28-day cycles 2, 1
3. Combination therapy: Preferably with dexamethasone (40 mg on days 1-4,9-12,17-20 in odd months and days 1-4 in even months) 5
4. Duration: Continue until disease progression or unacceptable toxicity 1
5. Response assessment: Every 3-4 months with serum and urine electrophoresis 2

For Maintenance Therapy:

1. Start after achieving at least partial remission following autologous stem cell transplantation 2
2. Lower dose regimen: 50-100 mg/day to minimize long-term toxicity 3, 4
3. Continue until disease progression or unacceptable toxicity 2

Adverse Effects and Management

Thromboembolism Risk

• Significant risk of deep vein thrombosis (up to 5% per month), especially when combined with dexamethasone 1
• Mandatory antithrombotic prophylaxis for patients with risk factors (high tumor burden, history of thrombosis) 2, 1

Peripheral Neuropathy

• Frequent sensorimotor neurological defects that can be irreversible 1
• Baseline neurological examination and regular monitoring required 1
• Consider dose reduction (to 50-100 mg/day) or discontinuation if neuropathy develops 3, 4

Other Common Side Effects

• Constipation, fatigue, sedation, and rash 4
• Neutropenia when used in combination therapy 4

Monitoring Recommendations

1. Baseline assessment: Neurological examination, thromboembolism risk factors, pregnancy test in women of childbearing age 1
2. Regular follow-up: Every 3-4 months with complete blood count, serum and urine electrophoresis, creatinine, and calcium 2
3. Neurological assessment: Regular monitoring for signs of peripheral neuropathy 1
4. Skeletal evaluation: X-ray or MRI for bone pain to detect new lesions 2

Special Considerations

• Lower doses (50-100 mg/day) may be equally effective with better tolerability, especially for long-term use 3, 4
• Strict pregnancy prevention required due to teratogenicity 1, 6
• Adequate hydration (3 L/day) recommended for patients with renal insufficiency 1

Comparative Efficacy

• Median time to progression with thalidomide/dexamethasone as primary therapy is approximately 18 months 5
• Novel agent combinations (thalidomide or bortezomib plus dexamethasone) are superior to the classical VAD regimen 2
• Thalidomide analogs like pomalidomide may offer better safety profiles for certain patients 6, 7

Thalidomide has revolutionized multiple myeloma treatment but requires careful patient selection and monitoring due to its significant adverse effect profile, particularly thromboembolism and peripheral neuropathy.