A Combination of Melphalan, Prednisone, and 50 mg Thalidomide Treatment in Non-Transplant-Candidate Patients with Newly Diagnosed Multiple Myeloma
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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 firstline 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.
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 firstline 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.
참고문헌 (21)
- Kyle R A, "Multiple myeloma", N Engl J Med, 351, pp.1860~1873 (2004)
- Phekoo KJ, "A population study to define the incidence and survival of multiple myeloma in a National Health Service Region in UK", Br J Haematol, 127, pp.299~304 (2004)
- Kim HJ, "Multiple myeloma in Korea: clinical analysis and treatment results in 61 cases", Korean J Intern Med, 2, pp.120~124 (1987)
- 이재훈, "한국인 다발성 골수종의 역학 변화", 대한혈액학회지, 41(4), pp.1~1 (2006), 대한혈액학회
- Palumbo A, "Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial", Lancet, 367, pp.825~831 (2006)
- Hulin C, "Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01", 01 trial, 2009, pp.27, 3664~3670
- Wijermans P, "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, 28, pp.3160~3166 (2010)
- Facon T, "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, 370, pp.1209~1218 (2007)
- Yakoub-Agha I, "Thalidomide in patients with advanced multiple myeloma: a study of 83 patients- -report of the Intergroupe Francophone du Myelome (IFM)", Hematol J, 3, pp.185~192 (2002)
- Attal M, "A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma: intergroupe Francais du Myelome", N Engl J Med, 335, pp.91~97 (1996)
- Qazilbash MH, "Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma", Bone Marrow Transplant, 39, pp.279~283 (2007)
- "Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists’ Collaborative Group", J Clin Oncol, 16, pp.3832~3842 (1998)
- Waage A, "Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma", Blood, 116, pp.1405~1412 (2010)
- Singhal S, "Antitumor activity of thalidomide in refractory multiple myeloma", N Engl J Med, 341, pp.1565~1571 (1999)
- Hus I, "An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma", Br J Cancer, 91, pp.1873~1879 (2004)
- Steurer M, "Low-dose thalidomide for multiple myeloma: interim analysis of a compassionate use program", Onkologie, 27, pp.150~154 (2004)
- Harousseau JL, "The role of complete response in multiple myeloma", Blood, 114, pp.3139~3146 (2009)
- El Accaoui RN, "Thalidomide and thrombosis: a meta-analysis", Thromb Haemost, 97, pp.1031~1036 (2007)
- Koh Y, "Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide", ANNALS OF HEMATOLOGY, 89(2), pp.201~206 (2010), SPRINGER
- San Miguel JF, "Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma", N Engl J Med, 359, pp.906~917 (2008)
- Zonder JA, "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, placebocontrolled SWOG trial S0232", Blood, 110, pp.77~ (2007)