Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation

• Published in: Blood 2011-08, Vol.118 (5), p.1231-1238
• Main Authors: Morgan, Gareth J., Davies, Faith E., Gregory, Walter M., Russell, Nigel H., Bell, Sue E., Szubert, Alexander J., Coy, Nuria Navarro, Cook, Gordon, Feyler, Sylvia, Byrne, Jenny L., Roddie, Huw, Rudin, Claudius, Drayson, Mark T., Owen, Roger G., Ross, Fiona M., Jackson, Graham H., Child, J. Anthony
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Clinical Trials and Observations; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Eligibility Determination; Female; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoid Neoplasia; Male; Medical sciences; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - therapy; Neoadjuvant Therapy; Patient Selection; Thalidomide - administration & dosage; Thalidomide - adverse effects; Transplantation, Autologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-02-338665

As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.