A Combination of Melphalan, Prednisone, and 50 mg Thalidomide Treatment in Non-Transplant-Candidate Patients with Newly Diagnosed Multiple Myeloma
Hye Jung Chang,1Jae Hoon Lee,2Young Rok Do,3Sung-Hwa Bae,4Jung-Lim Lee,5Seung Hyun Nam,6Sung-Soo Yoon,7
and Soo-Mee Bang1
1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
2Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea.
3Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.
4Department of Internal Medicine, Catholic University of Daegu, Daegu, Korea.
5Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea.
6Department of Internal Medicine, Seoul Veterans Hospital, Seoul, Korea.
7Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Correspondence to Soo-Mee Bang, M.D. Department of Internal Medicine, Seoul National University Bundang Hospital, Gumi-dong, Bundang-gu, Seongnam 463-707, Korea. Tel: 82-31-787-7039, Fax: 82-31-787-4052, Email: smbang7@snu.ac.kr
Received December 22, 2010; Revised April 05, 2011; Accepted May 13, 2011.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a first-line treatment. Because the side effects of thalidomide at a dose of ≥ 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates.
Methods
Twenty-one patients were treated in 4-week cycles, receiving 4 mg/m2 melphalan and 40 mg/m2 prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism.
Results
The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy.
Conclusions
Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.
Algorithm for patient enrollment, according to expected response
CR, complete response; PR, partial response.
References
1.
Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860–1873.
2.
Phekoo KJ, Schey SA, Richards MA, et al. A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK. Br J Haematol 2004;127:299–304.
3.
Kim HJ, Heo DS, Bang YJ, et al. Multiple myeloma in Korea: clinical analysis and treatment results in 61 cases. Korean J Intern Med 1987;2:120–124.
4.
Lee JH, Bang SM. Epidemiological change of multiple myeloma in Korea. Korean J Hematol 2006;41:225–234.
5.
Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006;367:825–831.
6.
Hulin C, Facon T, Rodon P, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 2009;27:3664–3670.
7.
Wijermans P, Schaafsma M, Termorshuizen F, et al. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol 2010;28:3160–3166.
8.
Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007;370:1209–1218.
9.
Yakoub-Agha I, Attal M, Dumontet C, et al. Thalidomide in patients with advanced multiple myeloma: a study of 83 patients--report of the Intergroupe Francophone du Myelome (IFM). Hematol J 2002;3:185–192.
10.
Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma: intergroupe Francais du Myelome. N Engl J Med 1996;335:91–97.
11.
Qazilbash MH, Saliba RM, Hosing C, et al. Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma. Bone Marrow Transplant 2007;39:279–283.
12.
Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998;16:3832–3842.
13.
Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010;116:1405–1412.
14.
Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341:1565–1571.
15.
Hus I, Dmoszynska A, Manko J, et al. An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma. Br J Cancer 2004;91:1873–1879.
16.
Steurer M, Spizzo G, Mitterer M, Gastl G. Low-dose thalidomide for multiple myeloma: interim analysis of a compassionate use program. Onkologie 2004;27:150–154.
17.
Harousseau JL, Attal M, Avet-Loiseau H. The role of complete response in multiple myeloma. Blood 2009;114:3139–3146.
18.
El Accaoui RN, Shamseddeen WA, Taher AT. Thalidomide and thrombosis: a meta-analysis. Thromb Haemost 2007;97:1031–1036.
19.
Koh Y, Bang SM, Lee JH, et al. Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide. Ann Hematol 2010;89:201–206.
20.
San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906–917.
21.
Zonder JA, Crowley J, Hussein MA, et al. Superiority of lenalidomide (Len) plus high-dose dexamethasone (HD) compared to HD alone as treatment of newly-diagnosed multiple myeloma (NDMM): results of the randomized, double-blinded, placebo-controlled SWOG trial S0232. Blood 2007;110:77.
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