ABSTRACT Introduction: We report the results of a prospective study of long-tern treatment with single-agent thalidomide in patients who had responded in a preceding trial of the use of thalidomide for relapsed/refractory myeloma. Patients and Methods: Nineteen patients were enrolled: 11 patients (57.9%) treated at a dosage of 100 mg/day; 2 patients (10.5%) at a dosage of 200 mg/day; 2 patients (10.5%) at a dosage of 300 mg/day; and 4 patients (21.1%) at a dosage of 400 mg/day. The median follow-up from the start of the preceding study was 3.0 years. At the time of entry to this study, 5 patients (26.3%) had partial response (PR), another 5 patients (26.3%) had a minimal response (MR), and the remaining 9 patients (47.4%) had shown no change (NC). Results: The cumulative MR rate was 78.9% (at the 32nd week) and the cumulative PR rate was 47.4% (at the 112th week). The median progression-free survival was 104 weeks and the median time to next treatment was 144 weeks. No patients experienced grade 4 or greater hematologic toxicity or grade 3 or greater non-hematologic toxicity. Conclusion: Long-term thalidomide maintenance therapy induced an increase in response rate, suppressed the progression to active myeloma without severe adverse events, and contributed to long survival with good activities of daily living.
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nullK. Shimizu, H. Murakami, M. Sawamura, Y. Hattori, S. Okamoto, A. Miwa, I. Sugiura, C. Shimazaki, M. Taniwaki, T. Ishida, T. Hayashi, H. Kosugi, M. Yuge, S. Iida, T. Ishida, K. Sunami, H. Asaoku, A. Sakai, M. Abe and T. Takagi, "Efficacy of Long-Term Treatment with Low-Dose Thalidomide for Patients with Relapsed/Refractory Multiple Myeloma," International Journal of Clinical Medicine, Vol. 2 No. 5, 2011, pp. 570-575. doi: 10.4236/ijcm.2011.25094.
 M. Attal, J. L. Harousseau, S. Leyvraz, C. Doyen, C. Hulin, L. Benboubker, I. Y. Agha, J.H. Bourhis, L. Garderet, B. Pegourie, C. Dumontet, M. Renaud, L. Voillat, C. Berthou, G. Marit, M. Monconduit, D. Caillot, B. Grobois, H. Avet-Loiseau, P. Moreau and T. Facon, “Maintenance Therapy with Thalidomide Improves Survival in Patients with Multiple Myeloma,” Blood, Vol. 108, No. 10, 2006, pp. 3289-3294. doi:10.1182/blood-2006-05-022962
 A. Spencer, H. Miles-Prince, A. W. Roberts, I. W. Prosser, K. F. Bradstock, L. Coyle, D. S. Gill, N. Horvath, J. Reynolds and N. Kennedy, “Consolidation Therapy with Low-Dose Thalidomide and Prednisolone Prolongs the Survival of Multiple Myeloma Patients Undergoing a Single Autologous Stem-Cell Transplantation Procedure,” Journal of Clinical Oncology, Vol. 27, No. 11, 2009, pp. 1788-1793. doi:10.1200/JCO.2008.18.8573
 B. Barlogie, G. Tricot, E. Anaissie, J. Shaughnessy, E. Rasmussen, F. van Rhee, A. Fassas, M. Zangari, K. Hollmig, M. Pineda-Roman, C. Lee, G. Talamo, R. Thertulien, E. Kiwan, S. Krishna, M. Fox and J. Crowley, “Thalidomide and Hematopoietic-Cell Transplantation for Multiple Myeloma,” The New England Journal of Medicine, Vol. 354, No. 10, 2006, pp. 1021-1030.
 G. J. Morgan, F. E. Davies, W. M. Gregory, S. E. Bell, A J. Szubert, K. Cocks, N. N. Coy, M. T. Drayson, R. G. Owen, F. M. Ross, G. H. Jackson and J. A. Child, “The Addition of Thalidomide to the Induction Treatment of Newly Presenting Myeloma Patients Increase the CR Rate Which Is Likely to Translate into Improved PFS and OS,” Blood, Vol. 114, No. 22, 2009; p. 114.
 H. M. Lokhorst, .B van der Holt, S. Zweegman, E. Vellenga, S. Croockewit, M. H. van Oers, P. von dem Borne, P. Wijermans, R. Schaafsma, O. de Weerdt, S. Wittebol, M. Delforge, H. Berenschot, G. M. Bos, K.-S. G. Jie, H. Sinnige, M. van Marwijk-Kooy, P. Joosten, M. C. Minnema, R. van Ammerlaan and P. Sonneveld, “A Randomized Phase III Study on the Effect of Thalidomide Combined with Adriamycin, Dexamethasone (TAD), and High-Dose Melphalan, Followed by Thalidomide Maintenance in Patients with Multiple Myeloma,
 A. Glasmacher, C. Hahn, F. Hoffmann, R. Neumann, H. Goldschmidt, M. von Lilienfeld-Toal, K. Orlopp, I. Schmidt-Wolf and M. Gorschlüter, “A Systematic Review of Phase-II Trials of Thalidomide Monotherapy in Patients with Relapsed or Refractory Multiple Myeloma,” British Journal of Haematology, Vol. 132, No. 5, 2006, pp. 584-593.
 S. Feyler, A. Rawstron, G. Jackson, J. A. Snowdon, K. Cocks and R. J. Johnson, “Thalidomide Maintenance Following High-Dose Therapy in Multiple Myeloma: A UK Myeloma Forum Phase II Study,” British Journal of Haematology, Vol. 139, No. 3, 2007, pp. 429-433.
 H. Murakami, K. Shimizu, M. Sawamura, K. Suzuki, I. Sugiura, H. Kosugi, C. Shimazaki, M. Taniwaki, M. Abe, and T. Takagi, “Phase II and Pharmacokinetic Study of Thalidomide in Japanese Patients with Relapsed/Refractory Multiplemyeloma,” International Journal of Hematology, Vol. 89, No. 5, 2009, pp. 636-641.
 J. Bladé, D. Samson, D. Reece, J. Apperley, B. Bjorkstrand, G. Gahrton, M. Gertz, S. Giralt, S. Jagannath and D. Vesole, “Criteria for Evaluating Disease Response and Progression in Patients with Multiple Myeloma Treated by High-Dose Therapy and Haemopoietic Stem Cell Transplantation,” British Journal of Haematology, Vol. 102, No. 5, 1998, pp. 1115-1123.
 S. Singhal, J. Mehta, R. Desikan, D. Ayers, P. Roberrson, P. Eddlemon, N. Munshi, E. Anaissie, C. Wilson, M. Dhodapkar, J. Zeldis and B. Barlogie, “Antitumor Activity of Thalidomide in Refractory Multiple Myeloma,” The New England Journal of Medicine, Vol. 341, No. 21, 1999, pp. 1565-1571. doi:10.1056/NEJM199911183412102
 H. M. Prince, B. Schenkel and L. Mileshkin, “An Analysis of Clinical Trials Assessing the Efficacy and Safety of Single-Agent Thalidomide in Patients with Relapsed or Refracttory Multiple Myeloma,” Leukemia & Lymphoma, Vol. 48, No. 1, 2007, pp. 46-55.
 A. Corso, P. Zappasodi, L. Barbarano, M. T. Petrucci, A. Palumbo, T. Caravita, S. Mangiacavalli, A. M. Cafro, M. Varettoni, F. Gay, E. Morra and M. Lazzarino, “Long-Term Outcome in Relapsed and Refractory Multiple Myeloma Treated with Thalidomide. Balancing Efficacy and Side-Effects,” Leukemia Research, Vol. 33, No. 9, 2009, pp. 145-149. doi:10.1016/j.leukres.2009.03.015
 A. A. Chanan-Khan and S. Giralt, “Importance of Achieving a Complete Response in Multiple Myeloma and the Impact of Novel Agents,” Journal of Clinical Oncology, Vol. 28, No. 15, 2010, pp. 2612-2624.
 J. Haessler, J. D. Shaughnessy, F. Zhan, J. Crowley, J. Epstein, F. van Rhee, E. Anaissie, M. Pineda-Roman, M. Zangari, K. Hollmig, A. Mohiuddin, Y. Alsayed, A. Hoering, G. Tricot and B. Barlogie, “Benefit of Complete response in Multiple Myeloma Limited to High-Risk Subgroup Identified by Gene Expression Profiling,” Clinical Cancer Research, Vol. 13, No. 23, 2007, pp. 7073-7079.
 B. Barlogie, E. Anaissie, J. Haessler, F. van Rhee, M. Pineda-Roman, K. Hollmig, Y. Alsayed, J. Epstein, J. D. Shaughnessy Jr and J. Crowley, “Complete Remission Sustained 3 Years from Treatment Initiation Is a Powerful Surrogate for Extended Survival in Multiple Myeloma,” Cancer, Vol. 113, No. 2, 2008, pp. 355-359.
 B. G. Durie, J. L. Harousseau, S. J. Miguel, J. Blade, B. Barlogie, K. Anderson, M. Gertz, M. Dimopoulos, J. Westin, P. Sonneveld, H. Ludwig, G. Gahrton, M. Beksac, J. Crowley, A. Belch, M. Boccadaro, M. Cavo, I. Turesson, D. Joshua, D. Vesole, R. Kyle, R. Alexanian, G. Tricot, M. Attal, G. Merlini, R. Powles, P. Richardson, K. Shimizu, P. Tosi, G. Morgan and S. V. Rajkumar, “International Uniform Response Criteria for Multiple Myeloma,” Leukemia, Vol. 20, No. 9, 2006, pp. 1467-1473.
 A. K. Stewart, “Novel Therapies for Relapsed Myeloma,” Hematology 2009 American Society of Hematology Education Program, Scottsdale, 2009, pp. 578-586.
 L. Mileshkin and H. M. Prince, “The Troublesome Toxicity of Peripheral Neuropathy with Thalidomide,” Leukemia & Lymphoma, Vol. 47, No. 11, 2006, pp. 2276- 2279. doi:10.1080/10428190600948303