Treatment: Multiple Myeloma

About 10% of pts have very slowly progressive disease (the so-called smoldering myeloma) and do not require treatment until the paraprotein levels rise above 50 g/L or progressive bone disease occurs. Pts with solitary plasmacytoma and extramedullary plasmacytoma are usually cured with localized radiation therapy. Supportive care includes early treatment of infections; control of hypercalcemia with glucocorticoids, hydration, and natriuresis; chronic administration of bisphosphonates to antagonize skeletal destruction; and prophylaxis against urate nephropathy and dehydration. Therapy aimed at the tumor is usually palliative. Initial therapy is usually one of several approaches, based on whether the pt is a candidate for high-dose therapy and autologous stem cell transplant. Transplant eligible (avoid alkylating agents): thalidomide, 400 mg/d PO or 200 mg qhs, plus dexamethasone, 40 mg/d on days 1-4 each month, with or without bortezomib, or chemotherapy such as liposomal doxorubicin. Transplant ineligible: melphalan, 8 mg/m² orally for 4-7 days every 4-6 weeks, plus prednisone. About 60% of pts have significant symptomatic improvement plus a 75% decline in the M component. Bortezomib also appears to improve response rates to melphalan. Experimental approaches using sequential high-dose pulses of melphalan plus two successive autologous stem cell transplants have produced complete responses in about 50% of pts <65 years. Long-term follow-up is required to see whether survival is enhanced. Palliatively treated pts generally follow a chronic course for 2-5 years, followed by an acceleration characterized by organ infiltration with myeloma cells and marrow failure. More aggressive treatment may produce median survival of 6 years. New approaches to salvage treatment include bortezomib, 1.3 mg/m² on days 1, 4, 8, and 11 every 3 weeks, often used with dexamethasone, vincristine, and/or liposomal doxorubicin. Lenalidomide is also active and increasingly used as maintenance therapy.