Disease progression

• Patients who achieve a durable response (>12 months) to initial therapy may respond to further treatment with the same regimen (response rate 25-50%).

• Patients who relapse early after initial therapy with M&P or fail to respond at relapse may respond to single agent dexamethasone (20-40mg/day x 4 days weekly x 3 weeks/month initially) or thalidomide (50-200mg/day) or these drugs in combination (response rate up to 70%) to which may be added cyclophosphamide (300-500mg/week) or clarithromycin (4 responses).

• Thalidomide (50-400mg/day) as a single agent achieves up to 30% responses in chemotherapy-resistant myeloma; addition of dexamethasone (20-40mg/day x 4 days/month) 4 response rates (up to 70%); side effects constipation, tremor, headache, oedema, somnolence; thromboembolism risk esp. in combination with anthracyclines (full dose warfarin or LMW heparin prophylaxis advised).

• Patients who relapse after prolonged response to HDM (>18 months) with a PBSC harvest sufficient for 2 procedures or with a further successful harvest may benefit from second HDM ± re-induction with VAD.

• There is evidence of a graft-versus-myeloma effect and DLI has re-induced responses in patients with recurrence after allogeneic SCT.

• The immunomodulatory drug Revimid and the proteosome inhibitor Velcade are both active in refractory and resistant myeloma; studies to define the role of these agents are in progress.

• Cyclophosphamide (50-100mg/day PO) is well tolerated palliative therapy for patients with advanced refractory disease or cytopenia who are intolerant of thalidomide or dexamethasone.

1 Child, J.A. et al. (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med, 348, 1875-1883.

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