Managed Care - July 2008 - (Page H12) TABLE Response rates* with MP, MPT, and MEL100/ASCT in newly diagnosed elderly MM patients % of patients (at 12 months) Response category Complete response ≥90% ≥50% MP (n=196) 2 8 40 MPT (n=125) 16 50 81 MEL 100 (n=126) 17 43 73 P value <.0001 <.0001 <.0001 *At final analysis, median follow-up time was 37 months. MEL100/ASCT=reduced intensity stem-cell transplantation after melphalan 100 mg/m2, MM=multiple myeloma, MP=melphalan and prednisolone, MPT=melphalan and prednisolone with thalidomide. Source: Facon 2007 and failed one prior therapy; however, as with thalidomide, its significant success in relapsed patients led to its clinical testing in those who are newly diagnosed. It has been shown that lowering the dexamethasone dose given with lenalidomide in newly diagnosed patients not only reduces side effects, but also improves survival (Rajkumar 2007). Unprecedented response rates of greater than 90 percent have been seen with lenalidomide and dexamethasone in this group of patients, with relatively low rates of toxicity (Rajkumar 2005, Lacy 2006). In general, lenalidomide is better tolerated than thalidomide, with significantly lower rates of neuropathy. Although lenalidomide is associated with an increased risk of myelosuppression and thromboembolic events, particularly DVT, these adverse events generally have proven to be manageable, especially with lower doses of dexamethasone (Zonder 2006, Shah 2007). Bortezomib (Velcade), a proteasome inhibitor with proapoptotic and antiangiogenic activity, is another novel agent that has undergone significant testing in the relapsed and frontline settings. Bortezomib was recently FDA approved as first-line therapy in the treatment of patients with multiple myeloma. Bortezomib-based therapies have shown consistently high response rates compared with conventional therapies when used as induction regimens for patients undergoing transplantation. In a single-center study of 38 patients, bortezomib in combination with thalidomide and dexamethasone resulted in a response rate of 92 percent and a CR of 18 percent (Wang 2005). Study responses were achieved rapidly and reduced the amount of therapy needed prior to ASCT. Bortezomib also has shown promise in conjunction with doxorubicin and dexamethasone prior to ASCT (Oakervee 2005). A reported drawback of bortezomib is peripheral neuropathy that can require treatment discontinuation (bortezomib 2008). Bortezomib is unavailable in oral form. Induction therapy, nontransplant candidates Until recently, the combination of melphalan and prednisone (MP) has been the standard treatment for elderly patients or for those patients who are otherwise ineligible for transplantation. This combination is now used much less often because of newer, more effective, and less toxic agents that can be used alone or in combination with melphalan or other agents. Recent research has shown that the addition of thalidomide to standard treatment with MP (MPT) may improve response rates, including CR, and may extend progression-free survival (PFS) and overall survival (OS) in newly diagnosed elderly patients (Table). In a study known as MEL100, 447 newly diagnosed myeloma patients between the ages of 65 and 75 were randomized to 1 of 3 treatment groups. The first received treatment with standard MP, the second with MPT, and the third with two sequential reduced-intensity stem-cell transplantations after melphalan 100 mg/m² (Facon 2007). Looking at the primary endpoint, OS, at a median follow-up of 51.5 months, patients on the MPT regimen fared better than those in the two other treatment groups. Patients receiving MEL100 and MP had similar rates of OS. Median OS for patients receiving MPT was 51.6 months, compared with 33.2 months for those receiving MP and 38.3 months for the MEL100 group. PFS and response also were better among patients receiving MPT. Toxic effects were more common with MPT than with the MP, but were lower than those noted with MEL100. The higher incidence in the MPT group, however, appeared to be counterbalanced by a low incidence of toxicity and early deaths (Facon 2007). Maintenance therapy All patients with myeloma, even those who achieve a CR or very good partial response (VGPR) during induction, eventually relapse. The goal of maintenance 12 MANAGED CARE / SUPPLEMENT
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