Randomized studies comparing standard-dose therapy to high-dose melphalan therapy (HDT) with hematopoietic stem cell support have shown that HDT can achieve high overall response rates and prolonged progression-free and overall survival; however, few, if any, patients are cured. | Chapter 106. Plasma Cell Disorders Part 8 Randomized studies comparing standard-dose therapy to high-dose melphalan therapy HDT with hematopoietic stem cell support have shown that HDT can achieve high overall response rates and prolonged progression-free and overall survival however few if any patients are cured. Although complete responses are rare 5 with standard-dose chemotherapy HDT achieves 2540 complete responses. In randomized studies HDT produced better median event-free survival in four of five studies higher complete response rate in four of five trials and better overall survival in three of five studies. Two successive HDTs tandem transplants are more effective than single HDT in the subset of patients who do not achieve a complete or very good partial response to the first transplant. Allogeneic transplants may also produce high response rates but treatment-related mortality may be as high as 40 . Non-myeloablative allogeneic transplantation is now under evaluation to reduce toxicity while permitting an immune effect. There is no standard maintenance therapy to prolong time to progression. IFN-a has allowed modest benefit but has significant side effects. Oral prednisone maintenance therapy was effective in a single trial. Ongoing studies are evaluating maintenance thalidomide and lenalidomide to prolong progression-free survival post-transplant. Relapsed myeloma can be treated with novel agents including lenalidomide and or bortezomib. These agents target not only the tumor cell but also the tumor cell-bone marrow interaction and the bone marrow milieu. These agents in combination with dexamethasone can achieve up to 60 partial responses and 1015 complete responses in patients with relapsed disease. The combination of bortezomib and liposomal doxorubicin is active in relapsed myeloma. Thalidomide if not used as initial therapy can achieve responses in refractory cases. High-dose melphalan and stem cell transplant if not used earlier
