Abstract
In the last two decades, we have seen a radical change in the therapy and prognosis of Multiple Myeloma (MM). Recent research on the role of the bone marrow microenvironment as integrant part of the biology of MM and the possible therapeutic interference at this level are leading to control and regression of the malignant plasma cell clone with a recognized clinical impact. Thalidomide, an old drug thought to interfere on the bone marrow microenvironment, is active not only for the treatment of refractory patients but also, as was recently shown, for induction and/or remission maintenance therapy. Most of the side effects (somnolence, constipation, fatigue, tremor, bradycardia, edema, and neuropathy) can be managed by reducing the dose and most patients need a dose reduction. The appropriate dose of thalidomide in myeloma is unknown. We treated thirty-five patients with MM with low-dose thalidomide (200mg or less). Twenty four patients were on maintenance therapy (13 after bone marrow transplantation, and 11 after chemotherapy with VCAP/VMCP); 5 patients were treated after relapse, 4 with refractory disease and 2 for remission induction as a first line therapy. Patients were treated at the Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre, RS, Brazil, from march/2001 to December/2003. The response as measured by hemoglobin level, immunoglobulin (M component) or urinary light chain concentration and bone marrow examination was evaluated before, 3, 6, and 12 months after the beginning of thalidomide.
Results: All patients are alive and well. Fifty one percent are on 100mg schedule; of the patients on maintenance therapy 90% are on complete remission or on a sustained plateau. A Wilcoxon ranks test for the immunoglobulin level before and after 6 months for the entire group showed p=0.001 (25–75%).
Conclusion: Low dose thalidomide is tolerable and effective.
Exosomes in the Pathogenesis and Treatment of Multiple Myeloma in the Context of the Bone Marrow Microenvironment