Multiple Myeloma: A Practical Guide to Current Management

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Multiple Myeloma: A Practical Guide to Current Management INTRODUCTION 4 Multiple myeloma is the second most common hematologic malignancy after non-Hodgkin’s lymphoma. It is estimated that 15,980 new cases of multiple myeloma (approximately 8,600 men and 7,380 women) will be diagnosed during 2005 in the United States, and approximately 11,300 individuals (5,660 men and 5,640 women) will die of the disease. The 5-year survival rate for patients with multiple myeloma is 30%, with younger patients having outcomes superior to those seen in the elderly. Although no cure exists for the disease, recent improvements in the treatment of multiple myeloma are expected to increase survival rates. The response of multiple myeloma to treatment is predominantly dependent on underlying genetic variation; nevertheless, commonly employed staging systems use more readily accessible clinical tools. Staging for multiple myeloma is commonly based on two approaches: The Durie-Salmon Staging (Appendix 1) and the recently proposed International Staging System (Appendix 2). Depending on the age of the patient and the disease stage, several treatment modalities are available for treating multiple myeloma, including: • Conventional-dose chemotherapy. • Steroid therapy. • High-dose chemotherapy with stem cell rescue. • Thalidomide-based regimens. • Newer agents: bortezomib and lenalidomide. Given the options available, treatment of multiple myeloma is dependent on individual physician pattern of practice, which is based on patient characteristics and clinical trials data for available therapies. These practices are reflected in these proceedings from a roundtable meeting entitled Multiple Myeloma: A Practical Guide to Current Management held on April 9, 2005, in conjunction with the 10 th International Myeloma Workshop in Sydney, Australia. Keith Stewart, MB.ChB., chaired the session and posed questions to experts in the field of multiple myeloma. The opinions of the experts are captured in this monograph.
Multiple Myeloma: A Practical Guide to Current Management OPTIMAL THERAPY FOR NEWLY DIAGNOSED PATIENT What constitutes optimal therapy for a patient newly diagnosed with multiple myeloma? Clinical practices among the participating experts varied with respect to the regimen of choice for treating multiple myeloma in the newly diagnosed patient. There was consensus that tumor burden and the perceived need for rapid cytoreduction were major factors influencing choice of initial therapy. Also, all agreed that candidates (generally those less than 70 years of age in good health) for consideration of auto-transplantation should not receive induction therapy with stem cell damaging agents (e.g., melphalan), which might preclude subsequent successful stem cell harvest. Traditionally, oncologists have used combination VAD chemotherapy as induction, but recently single-agent dexamethasone or dexamethasone with thalidomide have become popular due to convenience and avoidance of intravenous catheter use. Whether combination therapy with dexamethasone and thalidomide is now the “standard of care” for initial induction was raised as a question. In response, several participants indicated that single-agent dexamethasone induction therapy might be very reasonable in low-risk, low–tumorburden patients. In contrast, patients requiring rapid tumor burden control should receive combination therapy (dexamethasone and thalidomide or VAD). All participants, however, emphasized that, when combination therapy is chosen, careful attention to toxicities is imperative. Among the reasonable options for induction therapy given these caveats were single-agent dexamethasone and combination approaches including thalidomide plus dexamethasone, VAD (vincristine, doxorubicin, dexamethasone) and DVd (pegylated doxorubicin, vincristine and dexamethasone). For a non–transplantation population melphalan and prednisone remains the standard of care, although many clinicians are adopting the use of thalidomide/dexamethasone in this setting as well. The initial use of the thalidomide/dexamethasone combination in this setting is supported by data from two key studies that reported a favorable clinical outcome. The first study was from the Mayo Clinic [Rajkumar 2002], where 50 patients with newly diagnosed multiple myeloma were treated with thalidomide/dexamethasone. Thalidomide 200 mg/day was administered orally. Dexamethasone 40 mg/day was administered orally on days 1 to 4, 9 to 12, and 17 to 20 (odd cycles) and 40 mg/day on days 1 to 4 (even cycles), repeated monthly. A confirmed response rate of 64% (95% confidence interval [CI], 49% to 77%) was reported in 32 patients. The second study was from the M. D. Anderson Cancer Center [Weber 2003], where 40 consecutive patients with symptomatic multiple myeloma were given thalidomide 100 to 200 mg orally at bedtime, with serial increments of 50 to 100 mg at weekly intervals. Thalidomide was administered to a maximum tolerated dose of 400 mg. Dexamethasone 20 mg/m 2 was given for four days beginning on days 1, 9, and 17. Each cycle of treatment was considered to be 30 days. Both groups of patients were treated for at least three months. In this study also, 28 newly diagnosed patients were treated with thalidomide alone to a maximum tolerated dose of 600 mg. Of patients treated with thalidomide/ dexamethasone, 72% showed response to therapy (including complete response in 16% of patients), and the median time to remission was 0.7 months. Patients treated with thalidomide alone showed a 36% response rate and a median time to remission of 4.2 months. A recent update from the M.D. Anderson Cancer Center [Weber 2005] indicates a response rate of 69% in 130 patients who received thalidomide/dexamethasone. Median time to remission was 1.1 months and the median duration of remission had not yet been reached. Although the general consensus favors the combination of thalidomide and dexamethasone in cases of high tumor burden that merit a need for rapid cytoreduction, some participants supported the use of dexamethasone alone in patients with low disease burden. In such instances, addition of thalidomide is advocated in subsequent cycles of treatment if a suboptimal response is seen after one cycle of treatment with dexamethasone alone. 5
Page 1 and 2: Multiple Myeloma: A Practical Guide
Page 3 and 4: Introductory Letter Multiple Myelom
Page 5 and 6: Monograph Overview Target Audience:
Page 7: Faculty Disclosures Dr. Ivan Borrel
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