Thalidomide for Relapsed Myeloma Mayo Clin Proc, January 2003, Vol 78 34 Mayo Clin Proc. 2003;78:34-39 34 © 2003 Mayo Foundation for Medical Education and Research Original Article From the Division of Hematology and Internal Medicine (S.K., M.A.G., A.D., M.Q.L., R.F., S.R.H., J.A.L., R.A.K., P.R.G., T.E.W., S.V.R.) and Cancer Center Statistics (S.M.G., N.L.I.), Mayo Clinic, Rochester, Minn. This work was supported in part by grants CA93842, CA85818, and CA62242 from the National Cancer Institute, Bethesda, Md, and by the Celgene Corporation, Warren, NJ. Drs Rajkumar and Fonseca received Leukemia and Lymphoma Society of America Translational Research Awards. Dr Rajkumar is also supported by the Goldman Philanthropic Partnerships, Lake Forest, Ill, and the Multiple My- eloma Research Foundation. Address reprint requests and correspondence to S. Vincent Rajkumar, MD, Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: rajkumar.vincent@mayo.edu). Response Rate, Durability of Response, and Survival After Thalidomide Therapy for Relapsed Multiple Myeloma SHAJI KUMAR, MD; MORIE A. GERTZ, MD; ANGELA DISPENZIERI, MD; MARTHA Q. LACY, MD; SUSAN M. GEYER, PHD; NANCY L. ITURRIA, MS; RAFAEL FONSECA, MD; SUZANNE R. HAYMAN, MD; JOHN A. LUST, MD; ROBERT A. KYLE, MD; PHILIP R. GREIPP, MD; THOMAS E. WITZIG, MD; AND S. VINCENT RAJKUMAR, MD • Objective: To assess response rate, duration of re- sponse, progression-free survival, and toxicity of thalido- mide in patients with relapsed multiple myeloma. • Patients and Methods: Thirty-two patients with re- lapsed multiple myeloma were entered into the study be- tween April 29, 1999, and June 20, 2000. They were given oral thalidomide at a dosage of 200 mg/d for 2 weeks, which was then increased as tolerated to a maximum of 800 mg/d. The primary end point of the study was response rate. • Results: The median age of the patients was 67 years (range, 36-78 years). Prior chemotherapy had failed in all patients, and stem cell transplantation had failed in 5 pa- tients (16%). There were 10 confirmed responses, yielding a response rate of 31%. In addition, there was 1 uncon- firmed partial response and 7 minimal responses with no complete responses. The median duration of response was 11.9 months (range, 3.7-20.3 months). Overall, 20 patients have died, and 26 patients have experienced disease pro- gression. The median follow-up of surviving patients was 28.5 months (range, 19.3-34.0 months), with a median pro- gression-free survival of 8.6 months (95% confidence in- CI = confidence interval; CR = complete response; CTC = Common Toxicity Criteria; MM = multiple myeloma; M-pro- tein = monoclonal protein; PCLI = plasma cell labeling index; PFS = progression-free survival; PR = partial response; STEPS = System for Thalidomide Education and Prescribing Safety; TNF-α = tumor necrosis factor α terval [CI], 4.7-16 months). The median progression-free survival among the responding patients was 15.7 months (95% CI, 8.6-25.6 months). The median overall survival for the entire group was 22 months (95% CI, 10.6-35.9 months). The most common treatment-related nonhema- tologic toxic effects (grade >3) were neuropathy (16%), sedation (13%), febrile neutropenia (6%), and constipa- tion (6%). • Conclusions: Thalidomide is useful in the treatment of patients with relapsed multiple myeloma and produced durable response in approximately one third of patients, with median response duration of nearly 1 year. Mayo Clin Proc. 2003;78:34-39 M ultiple myeloma (MM) is characterized by a clonal proliferation of abnormal plasma cells in the bone marrow that results in a variety of different clinical mani- festations, including osteolytic bone lesions, which can lead to pathologic fractures, anemia, life-threatening hy- percalcemia, and renal failure. 1 It accounts for more than 10% of all hematologic malignancies and nearly 1% of all malignancies. An estimated 14,600 new patients will be diagnosed as having myeloma in the United States alone during 2002 and an estimated 10,800 deaths will be due to myeloma in that same period. 2 The median survival from diagnosis among patients treated with conventional chemotherapy is 3 to 4 years. 3 Introduction of high-dose chemotherapy with stem cell rescue has led to improved survival, but these patients eventually experience disease relapse. Multiple myeloma remains an incurable disease. 4 For editorial comment, see page 15. A large body of recent work showed a major role for bone marrow angiogenesis in the biology of this disease. 5-10 Studies have shown that the degree of marrow angiogen- esis is prognostic in these patients and correlates with measures of cell proliferation, such as the plasma cell labeling index (PCLI) and the stage of the disease. 7,11 The role of angiogenesis in the progression of malignancies provided the rationale for the use of antiangiogenic therapy for myeloma. 12 Thalidomide (α-N-[phthalimido] glutar- For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.