Mayo Clin Proc. • July 2004;79(7):867-874 • www.mayo.edu/proceedings 867 RELAPSED MULTIPLE MYELOMA ORIGINAL ARTICLE SHAJI K. KUMAR, MD; TERRY M. THERNEAU, PHD; MORIE A. GERTZ, MD; MARTHA Q. LACY, MD; ANGELA DISPENZIERI, MD; S. VINCENT RAJKUMAR, MD; RAFAEL FONSECA, MD; THOMAS E. WITZIG, MD; JOHN A. LUST, MD, PHD; DIRK R. LARSON, MS; ROBERT A. KYLE, MD; AND PHILIP R. GREIPP, MD Clinical Course of Patients With Relapsed Multiple Myeloma From the Division of Hematology and Internal Medicine (S.K.K., M.A.G., M.Q.L., A.D., S.V.R., T.E.W., J.A.L., R.A.K., P.R.G.) and Division of Biostatis- tics (T.M.T., D.R.L.), Mayo Clinic College of Medicine, Rochester, Minn; and Division of Hematology/ Oncology, Mayo Clinic College of Medicine, Scottsdale, Ariz (R.F.). Supported in part by Hematological Malignancies Fund, Mayo Foundation, National Cancer Institute (CA62242), and a research grant from Millennium Pharmaceuticals, Cambridge, Mass. Dr Greipp received honoraria for his participation on Millennium Pharmaceuticals’ advisory board. Individual reprints of this article are not available. Address correspondence to Philip R. Greipp, MD, Division of Hematology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905 (e-mail: greipp.philip@mayo.edu). © 2004 Mayo Foundation for Medical Education and Research OBJECTIVE: To study the clinical course of patients with multiple myeloma (MM) that relapses after initial therapy. PATIENTS AND METHODS : Patients with MM, seen at the Mayo Clinic in Rochester, Minn, between January 1, 1985, and Decem- ber 31, 1998, were identified from a prospectively maintained database. Our study population consisted of 578 patients with newly diagnosed MM who were followed up and monitored throughout their clinical course at our institution. RES ULTS : The median age of the 578 patients with MM was 65 years (range, 26-92 years); 228 patients (39%) were women. The median follow-up of 71 surviving patients was 55 months (range, 0-202 months). The overall survival (OS) for the 578 patients at 1, 2, and 5 years was 72%, 55%, and 22%, respectively; the median OS from initial therapy was 28.4 months. The median OS of 355 patients who experienced relapse after initial treatment was 17.1 months from initiation of the second therapy, and 84% died within 5 years. The duration of response decreased consistently with each successive regimen. Patients with a high plasma cell label- ing index ( ≥1.0%), low platelet count (<150 × 10 9 / L), high creati- nine level ( ≥ 2.0 mg/ dL), and low albumin level (<3.0 g/ dL) had a poorer prognosis. CONCLUS IONS : Our study revealed decreasing response duration with increasing number of salvage regimens, probably reflecting acquired drug resistance and an increasing proliferative rate of the myeloma cells. Patients who experienced relapse after initial treatment and received salvage therapy had a median survival of nearly 1.5 years. This must be remembered when making treat- ment decisions for these patients and must be factored in when assessing the efficacy of new therapies. M ayo Clin Proc. 2004;79(7):867-874 CI = confidence interval; M M = multiple myeloma; OS = overall survival; PCLI = plasma cell labeling index; RR = relative risk M ultiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of immunoglob- ulin-secreting plasma cells. Clinically, MM presents with anemia, renal insufficiency, hypercalcemia, and/or lytic bone lesions. Multiple myeloma accounts for 1% of all malignancies and 10% of hematologic malignancies. 1 The disease predominantly affects older individuals; the me- dian age at diagnosis is 65 years. Multiple myeloma re- sults in considerable morbidity and mortality among af- fected patients. Based on projections, 15,270 patients will be diagnosed as having MM and 11,070 will die of MM in 2004. 2 Since the introduction of melphalan and prednisone for treatment of myeloma 4 decades ago, multiple other che- motherapy combinations have been tried for the treatment of MM with better response rates but with no improvement in survival. 3 In a review of 1027 patients with newly diag- nosed MM seen at the Mayo Clinic in Rochester, Minn, between January 1, 1985, and December 31, 1998, no improvement in overall survival (OS) was observed. 4 How- ever, the OS was higher compared with a group of patients seen during a preceding period. 5 The median survival from diagnosis for the 1027 patients was 33 months. Several randomized trials of high-dose therapy with autologous stem cell transplantation vs standard combina- tion chemotherapy have shown improved OS with trans- plantation, especially in those younger than 65 years. 6,7 Median survival of 4 to 5 years has been observed in the transplantation trials. Recent trials have suggested a role for additional high-dose regimens or tandem transplanta- tion, which may further improve survival. 8,9 Unfortunately, most patients experience relapse after responding to initial therapies, including high-dose therapy and stem cell trans- plantation. Long-term remissions are rare. 10 Various sal- vage therapies have been tried for these patients including combination chemotherapy and allogeneic stem cell trans- plantation. Several agents are active in MM including alky- lating agents and corticosteroids, and it is not unusual for many patients with relapsed disease to receive several treatment regimens of 1 or more of these agents. 11 Unfortu- nately, the responses obtained from most of these ap- proaches are not durable. The clinical course of patients whose disease relapses after initial therapy has not been studied systematically with respect to the response and survival from each subse- quent therapy. The primary reason for this lack of complete data from diagnosis to death is because patients often are treated at various institutions during the course of disease. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.