Abstract
A prospective, multicenter, phase II study was performed to assess the efficacy and safety of thalidomide maintenance therapy at different doses in Japanese multiple myeloma (MM) patients. This study included 34 patients (median age, 74 years) who were previously treated with not more than three prior therapies and whose response status was evaluated as at least stable disease. They were randomized into Group A (no maintenance; 12 patients), Group B (50 mg thalidomide maintenance; 12 patients), and Group C (100 mg thalidomide maintenance; 10 patients), respectively. Thalidomide maintenance therapy resulted in improved depth of response in three cases (13.6%) and sustained response after induction therapy in eight cases (36.4%). Two-year progression-free survival (PFS) was 25.0%, 33.3%, and 77.8% in Groups A, B, and C, respectively, and was significantly higher in Group C than in Group A (p = 0.005). There was no difference in the incidence of hematological or non-hematological adverse events between Groups B and C. The current study demonstrates that maintenance with daily thalidomide at 100 mg, but not 50 mg, improved depth of response and prolonged PFS, and that this treatment was feasible for use in Japanese MM patients.
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22 May 2019
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References
Attal M, Harousseau J-L, Facon T, Guilhot F, Doyen C, Fuzibet J-G, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349:2495–502.
Ludwig H, Beksac M, Bladé J, Cavenagh J, Cavo M, Delforge M, et al. Multiple myeloma treatment strategies with novel agents in 2011: a European perspective. Oncologist. 2011;16:388–403.
Matsumura-Kimoto Y, Kuroda J, Kaneko H, Kamitsuji Y, Fuchida S, Nakaya A, et al. Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum. Int J Hematol. 2018;107:541–50.
Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60.
Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, FIRST Trial Team, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371:906–17.
Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Inter-Groupe Francophone du Myélome (IFM). Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.
Kalff A, Kennedy N, Smiley A, Prince HM, Roberts AW, Bradstock K, et al. Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study. Lancet Haematol. 2014;1:e112-9.
Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, et al. Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res. 2013;19:6030–8.
Barlogie B, Pineda-Roman M, van Rhee F, Haessler J, Anaissie E, Hollmig K, et al. Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood. 2008;112:3115–21.
Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit 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;115:1113–20.
Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, 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;27:1788–93.
Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008;112:3107–14.
Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Bjorkstrand B, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010;116:1405–12.
Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, 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;28:3160–6.
The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749–57.
Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, et al. International myeloma workshop consensus panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117:4691–5.
Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, IFM Investigators, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782–91.
McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770–81.
Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371:895–905.
Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366:1759–69.
Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, et al. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015;126:1294–301.
Acknowledgements
The authors would like to thank Dr. Kunihiko Hayashi of the Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, for comments on the statistical analysis. This study was supported by the Epidemiological and Clinical Research Information Network (ECRIN).
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Dr. Murakami H received a research grant from Fujimoto Pharmaceutical Co. Ltd. and Celgen Co. Ltd, and served on scientific advisory boards and speakers’ bureaus for Celgen Co. Ltd., Sanofi K.K., and Ono Pharmaceutical CO, Ltd. Dr. Kiguchi T received a research grant from Celgen Co. Ltd., Sanofi K.K., and Janssen Pharmaceutical K.K. Other authors have no conflict of interest.
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Murakami, H., Kasamatsu, T., Murakami, J. et al. Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study). Int J Hematol 109, 409–417 (2019). https://doi.org/10.1007/s12185-019-02607-z
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DOI: https://doi.org/10.1007/s12185-019-02607-z