Current therapy of refractory multiple myeloma

Induction therapy with standard regimens induces an average objective response (OR) rate (Southwest Oncology Group [SWOG] Criteria) of 40%-50% in patients with previously untreated multiple myeloma (MM) [1, 2]. The great majority of those who initially achieve remission eventually relapse, with less than 20% of patients being in ongoing remission at five years from time of initial therapy [1]. At least 30% of MM patients fail to adequately respond to induction chemotherapy [3, 4]. Patients may exhibit clinical deterioration, increasing paraprotein levels, increasing marrow suppression, refractory hypercalcemia or worsening renal failure while undergoing induction therapy. Patients who do not achieve an OR to induction therapy are sometimes described as "nonresponders." This group includes patients who are truly primarily resistant to front-line therapy, patients whose disease is in plateau phase at time of disease presentation, and patients who are slow responders to their induction therapy. The terms "refractory" or "advanced" are often applied to patients who have either primary resistant or relapsed disease. The lack of agreed terminology is a major stumbling block to data review and the logical planning of clinical studies. A classification of relapsed and resistant disease is proposed in Figure 1. Prolongation of median survival beyond one year in studies of therapy for refractory MM patients is rarely achieved [3-104]. Failure of current cytotoxic therapy has led to attempts to improve treatment by the investigation of mechanisms of cytotoxic drug resistance, the development of methods to identify drug-resistant MM cells, and attempts to either prevent or, once established, to circumvent drug resistance [105-109]. Recent data on cytotoxic and/or systemic radiation therapy will be reviewed.