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Table of Contents
Vol. 114, Suppl. 1, 2005
Issue release date: September 2005
Acta Haematol 2005;114:8–13
(DOI:10.1159/000087038)

Future Directions in Multiple Myeloma Treatment

Child J.A. · Russell N. · Sonneveld P. · Schey S.
aGeneral Infirmary and University of Leeds, Leeds; bMolecular Medical Sciences, Division of Haematology, Nottingham University Medical School, Nottingham, UK; cErasmus Medical Center Rotterdam, Rotterdam, The Netherlands; dGuy’s Hospital, St. Thomas’ Street, London, UK

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Abstract

Future therapy options for multiple myeloma may be directed at asymptomatic disease, as only symptomatic myeloma is treated currently. Additional genetic information from gene array analysis will mean that the identification of cases with poor prognosis will become more sophisticated. New markers are being discovered constantly, and these continuously change the picture regarding prognostic factors. More intensive treatment options increase the depth of remissions, thereby improving outcomes. In pilot studies, cyclophosphamide, thalidomide and dexamethasone (CTD) was a highly effective, well-tolerated regimen for patients refractory to initial therapy with VAD or with relapsed disease. It is being further evaluated as induction therapy in the current MRC Myeloma IX trial. Also under investigation is a small molecule derivative of thalidomide, CC-4047 (Actimid). It has between 1,000 and 10,000 times more potent antitumour necrosis factor alpha activity, with an additional immunomodulatory effect. It has been shown to be between 50 and 2,000 times more potent in the stimulation of T-cell proliferation and 50–100 times more potent in augmenting interleukin-2 and interferon-γ production. With many possible approaches to study and work through, future strategies will revolve around exploration of the effectiveness of combinations that incorporate new agents in various disease and treatment settings. The use of genetic profiles to further delineate groups for different treatment approaches should enable the introduction of patient-specific treatment programmes in the future.



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References

  1. 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;121:749–757.
  2. Greipp PR, San Miguel J, Durie BG, et al: International Staging System for Multiple Myeloma. J Clin Oncol 2005;23:3412–3420.
  3. Fenton JA, Pratt G, Rawstron AC, et al: Genomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism. Oncogene 2003;22:1103–1113.
  4. Fenton JA, Pratt G, Rothwell DG, et al: Translocation t(11;14) in multiple myeloma: Analysis of translocation breakpoints on der(11) and der(14) chromosomes suggests complex molecular mechanisms of recombination. Genes Chromosomes Cancer 2004;39:151–155.
  5. Garand R, Avet-Loiseau H, Accard F, et al: t(11;14) and t(4;14) translocations correlated with mature lymphoplasmacytoid and immature morphology, respectively, in multiple myeloma. Leukemia 2003;17:2032–2035.
  6. Davies FE, Forsyth PD, Rawstron AC, et al: The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. Br J Haematol 2001;112:814–849.
  7. Child J, Morgan G, Davies F, et al: High-dose chemotherapy with hemopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003;348:1875–1883.
  8. Rawstron AC, Davies FE, Dasgupta R, et al: Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation. Blood 2002;100:3095–3100.
  9. Kane R, Bross P, Farrell A, Pazdur R: Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 2003;8:508–513.
  10. Richardson PG, Schlossman RL, Weller E, et al: Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002;100:3063–3067.
  11. Schey SA, Fields P, Bartlett JB, et al: Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004;22:3269–3276.
  12. Corral L, Haslett P, Muller G, et al: Differential cytokine modulation and T cell activation by wo distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 1999;163:380–386.
  13. Haslett P, Corral L, Albert M, Kaplan G: Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998;187:1885–1892.
  14. Marriott J, Clarke I, Dredge K, et al: Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4+ and CD8+ T cells. Clin Exp Immunol 2002;130:75–84.


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