Effect of Thalidomide as First-line Therapy on Postrelapse Survival Rate of Multiple Myeloma: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 WANGPing ¹ , SHENGZhi-xin ² , SUBao-hua ² ,  RANXue-hong ²

1. Weifang Medical University, Weifang 261041, China;
2. Weifang People's Hospital, Weifang 261041, China;

Corresponding author：

RANXue-hong, Email: ranxuehong1967@sina.com

Keywords：

Multiple myeloma; Thalidomide; Postrelapse survival; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20160014

Video：

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Objective To systematically review the effect of thalidomide as first-line therapy on postrelapse survival rate of patients with multiple myeloma (MM). Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 1, 2007) and Web of Science were searched to collect randomized controlled trials (RCTs) about thalidomide as first-line therapy for MM from 2006 to 2011. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.1 software. Results A total of 16 RCTs involving 6097 patients were included. The results of meta-analysis showed that, compared with the chemotherapy alone group, early application of thalidomide could significantly decrease the postrelapse survival rate (HR=1.23, 95%CI 1.05 to 1.45, P=0.002). Subgroup analysis showed that, compared with the chemotherapy alone group, thalidomide maintenance therapy after autologous stem cell transplantation (ASCT) couldn’t decrease the postrelapse survival rate (HR=0.90, 95%CI 0.57 to 1.41, P=0.64), but thalidomide induction therapy before ASCT (HR=1.21, 95%CI 1.01 to 1.45, P=0.04) and thalidomide induction therapy before ASCT combined maintenance therapy after ASCT (HR=1.41, 95%CI 1.13 to1.76, P=0.002) could significantly decrease the postrelapse survival rate. Conclusion Current evidence shows that, thalidomide maintenance therapy after ASCT for MM is a better therapy regimen. It couldn’t decrease the survival rate after recurrence, but could increase the disease-free survival (DFS) and overall survival (OS) of patients with MM. Due to the limited quality of included studies, the above conclusion still needs to be verified by more high quality studies.

Citation： WANGPing, SHENGZhi-xin, SUBao-hua, RANXue-hong. Effect of Thalidomide as First-line Therapy on Postrelapse Survival Rate of Multiple Myeloma: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(1): 66-72. doi: 10.7507/1672-2531.20160014 Copy

1.	Hicks LK, Haynes AE, Reece DE, et al. Hematology Disease Site Group of the Cancer Care Ontario Program in Evidence-based Care. A meta-analysis and systematic review of thalidomide for patients with previously untreated multiple myeloma. Cancer Treat Rev, 2008, 34(5): 442-452.
2.	Kumar A, Hozo I, Wheatley K, et al. Thalidomide versus bortezomib based regimens as first-line therapy for patients with multiple myeloma: a systematic review. Am J Hematol, 2011, 86(1): 18-24.
3.	Palumbo A, Bringhen S, Liberati AM, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood, 2008, 112(8): 3107-3114.
4.	Ludwig H, Hajek R, Tóthová E, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood, 2009, 113(15): 3435-3442.
5.	Lokhorst HM, van der Holt B, Zweegman S, et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood, 2010, 115(6): 1113-1120.
6.	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(9594): 1209-1218.
7.	Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol, 2009, 27(11): 1788-1793.
8.	Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-ce stem-cell transplantation for multiple myeloma. N Engl J Med, 2006, 349(26): 2495-2502.
9.	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(22): 3664-3670.
10.	Rajkumar SV, Blood E, Vesole D, et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol, 2006, 24(3): 431-436.
11.	Rajkumar SV, Rosiñol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol, 2008, 26(13): 2171-2177.
12.	Beksac M, Haznedar R, Firatli-Tuglular T, et al. Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol, 2011, 86(1): 16-22.
13.	Kapoor P, Rajkumar SV, Dispenzieri A, et al. Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis. Leukemia, 2011, 25(4): 689-696.
14.	Fayers PM, Palumbo A, Hulin C, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood, 2011, 118(5): 1239-1247.
15.	Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood, 2010, 116(9): 1405-1412.
16.	Barlogie B, Tricot G, Anaissie E, et al. Tthalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med, 2007, 354(10): 1021-1030.
17.	Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood, 2008, 112(8): 3115-3121.
18.	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(19): 3160-3166.
19.	Sacchi S, Marcheselli R, Lazzaro A, et al. A randomized trial with melphalan and prednisone versus melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant. Leuk Lymphoma, 2011, 52(10): 1942-1948.
20.	Zervas K, Mihou D, Katodritou E, et al. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol, 2007, 18(8): 1369-1375.
21.	Mateos MV, Oriol A, Martínez-López J, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol, 2010, 11(10): 934-941.
22.	Morgan GJ,Davies FE, GregoryWM, RussellNH, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood, 2011, 118(5): 1231-1238.

1. Hicks LK, Haynes AE, Reece DE, et al. Hematology Disease Site Group of the Cancer Care Ontario Program in Evidence-based Care. A meta-analysis and systematic review of thalidomide for patients with previously untreated multiple myeloma. Cancer Treat Rev, 2008, 34(5): 442-452.
2. Kumar A, Hozo I, Wheatley K, et al. Thalidomide versus bortezomib based regimens as first-line therapy for patients with multiple myeloma: a systematic review. Am J Hematol, 2011, 86(1): 18-24.
3. Palumbo A, Bringhen S, Liberati AM, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood, 2008, 112(8): 3107-3114.
4. Ludwig H, Hajek R, Tóthová E, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood, 2009, 113(15): 3435-3442.
5. Lokhorst HM, van der Holt B, Zweegman S, et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood, 2010, 115(6): 1113-1120.
6. 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(9594): 1209-1218.
7. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol, 2009, 27(11): 1788-1793.
8. Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-ce stem-cell transplantation for multiple myeloma. N Engl J Med, 2006, 349(26): 2495-2502.
9. 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(22): 3664-3670.
10. Rajkumar SV, Blood E, Vesole D, et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol, 2006, 24(3): 431-436.
11. Rajkumar SV, Rosiñol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol, 2008, 26(13): 2171-2177.
12. Beksac M, Haznedar R, Firatli-Tuglular T, et al. Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol, 2011, 86(1): 16-22.
13. Kapoor P, Rajkumar SV, Dispenzieri A, et al. Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis. Leukemia, 2011, 25(4): 689-696.
14. Fayers PM, Palumbo A, Hulin C, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood, 2011, 118(5): 1239-1247.
15. Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood, 2010, 116(9): 1405-1412.
16. Barlogie B, Tricot G, Anaissie E, et al. Tthalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med, 2007, 354(10): 1021-1030.
17. Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood, 2008, 112(8): 3115-3121.
18. 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(19): 3160-3166.
19. Sacchi S, Marcheselli R, Lazzaro A, et al. A randomized trial with melphalan and prednisone versus melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant. Leuk Lymphoma, 2011, 52(10): 1942-1948.
20. Zervas K, Mihou D, Katodritou E, et al. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol, 2007, 18(8): 1369-1375.
21. Mateos MV, Oriol A, Martínez-López J, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol, 2010, 11(10): 934-941.
22. Morgan GJ,Davies FE, GregoryWM, RussellNH, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood, 2011, 118(5): 1231-1238.

Chinese Journal of Evidence-Based Medicine

Effect of Thalidomide as First-line Therapy on Postrelapse Survival Rate of Multiple Myeloma: A Meta-analysis

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