Treatment of multiple myeloma: a comprehensive review

Abstract

Multiple myeloma (MM) is a neoplastic plasma cell disorder that results in end-organ damage (hypercalcemia, renal insufficiency, anemia, or skeletal lesions). Patients should not be treated unless they have symptomatic (end-organ damage) MM. They should be classified as having high-risk or standard-risk disease. Patients are classified as high risk in the presence of hypodiploidy or deletion of chromosome 13 (del[13]) with conventional cytogenetics, the presence of t(4:14), t(14;16), t(14;20) translocations or del(17p) with fluorescence in situ hybridization. High-risk disease accounts for about 25% of patients with symptomatic MM. If the patient is deemed eligible for an autologous stem cell transplantation (ASCT), 3 or 4 cycles of lenalidomide and low-dose dexamethasone, or bortezomib and dexamethasone, or thalidomide and dexamethasone are reasonable choices. Stem cells should then be collected and one may proceed with an ASCT. If the patient has a complete response or a very good partial response (VGPR), the patient may be followed without maintenance therapy. If the patient has a less than VGPR, a second ASCT is encouraged. If the patient is in the high-risk group, a bortezomib-containing regimen to maximum response followed by 2 additional cycles of therapy is a reasonable approach. Lenalidomide and low-dose dexamethasone is another option for maintenance until progression. If the patient is considered ineligible for an ASCT, then melphalan, prednisone, and thalidomide is suggested for the standard-risk patient, and melphalan, prednisone, and bortezomib (MPV) for the high-risk patient. Treatment of relapsed or refractory MM is covered. The novel therapies-thalidomide, bortezomib, and lenalidomide-have resulted in improved survival rates. The complications of MM are also described. Multiple myeloma is a plasma cell neoplasm that is characterized by a single clone of plasma cells producing a monoclonal protein (M-protein). The malignant proliferation of plasma cells produces skeletal destruction that leads to bone pain and pathologic fractures. The M-protein might lead to renal failure, hyperviscosity syndrome, or through the suppression of uninvolved immunoglobulins, recurrent infections. Anemia and hypercalcemia are common complications.

Figure 1. Classification of Multiple Myeloma at Diagnosis Into High Risk or Standard Risk

^aPatients with t(4;14), β₂-microglobulin < 4 mg/L, and Hb ≥ 10 g/dL may have intermediate-risk disease. Abbreviations: FISH = fluorescence in situ hybridization; Hb = hemoglobin; MM = multiple myeloma; mSMART = Stratification for Myeloma and Risk-Adapted Therapy; PCLI = plasma cell labeling index From Mayo Clin Proc., with permission.

Figure 2. Algorithm Outlining the Current Approach to the Treatment of Newly Diagnosed Myeloma

Abbreviations: CR = complete response; MPT = melphalan/prednisone/thalidomide; VGPR = very good partial response

Figure 3. Overall Survival From Time of Posttransplantation Relapse Grouped by Whether Patients Received One of the New Drugs (Thalidomide, Bortezomib, or Lenalidomide) or Not

This research was originally published in Blood. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-20. © the American Society of Hematology.

Figure 4. Overall Survival of Multiple Myeloma From Time of Diagnosis Before and After 1996

This research was originally published in Blood. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-20. © the American Society of Hematology.