Lenalidomide (Revlimid, CC-5013) in myelodysplastic syndromes: Is it any good?
Tóm tắt
The myelodysplastic syndromes (MDS) can be divided into "early" and "advanced" disease by evaluation of prognostic variables such as the number of cytopenias, karyotype, and percentage of myeloblasts. Patients with an isolated interstitial deletion of chromosome 5q31 represent a distinct subset who may derive particular benefit from immunomodulatory drugs. Goals of therapy for early MDS focus on hematologic improvement and maximizing quality of life. Thalidomide, the prototype of the immunomodulatory drugs, yields major erythroid responses in some patients with early MDS, but doselimiting neurologic toxicities limit its potential clinical benefit. Lenalidomide, a more potent and non-neurotoxic derivative, has shown promising results in early MDS, yielding hematologic improvement in almost half of patients and transfusion independence with cytogenetic remissions in approximately two thirds of patients harboring the chromosome 5q31 deletion.
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Tài liệu tham khảo
Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982, 51:189–199.
Harris NL, Jaffe ES, Diebold J, et al.: The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 1999, 10:1419–1432.
Greenberg P, Cox C, LeBeau MM, et al.: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997, 89:2079–2088. The most widely accepted prognostic system in the myelodysplastic syndromes, based on an analysis of 816 patients.
Boultwood J, Lewis S, Wainscoat JS: The 5q-syndrome. Blood 1994, 84:3253–3260.
Allampallam K, Shetty V, Mundle S, et al.: Biological significance of proliferation, apoptosis, cytokines, and monocyte/macrophage cells in bone marrow biopsies of 145 patients with myelodysplastic syndrome. Int J Hematol 2002, 75:289–297.
Bellamy WT, Richter L, Sirjani D, et al.: Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood 2001, 97:1427–1434.
Kitajima S, Kudo Y, Ogawa I, Bashir T: Overexpression of tumor necrosis factor (TNF)-α and interferon (IFN)-γ by bone marrow cells from patients with myelodysplastic syndromes. Leukemia 1997, 12:2049–2054.
Cheson BD, Bennett JM, Kantarjian H, et al.: Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000, 96:3671–3674. The standard for clinical trial response criteria in MDS.
Cheson BD, Bennett JM, Kantarjian H, et al.: Myelodysplastic syndromes standardized response criteria: further definition. Blood 2001, 98:1985.
Hellstrom-Lindberg E, Schmidt-Mende J, Forsblom AM, et al.: Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol 1997, 99:344–351.
Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, et al.: A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 2003, 120:1037–1046. A useful algorithm to predict which patients will respond to growth factor stimulation.
Corral LG, Kaplan G: Immunomodulation by thalidomide and thalidomide analogues. Ann Rheum Dis 1999, 58(Suppl 1):I107-I113.
Davies FE, Raje N, Hideshima T, et al.: Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001, 98:210–216.
Geitz H, Handt S, Zwingenberger K: Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996, 31:213–221.
Parman T, Wiley MJ, Wells PG: Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat Med 1999, 5:582–585.
Raza A, Meyer P, Dutt D, et al.: Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood 2001, 98:958–965. The largest study of single agent thalidomide as a treatment of MDS.
Musto P, Falcone A, Sanpaolo G, et al.: Thalidomide abolishes transfusion-dependence in selected patients with myelodysplastic syndromes. Haematologica 2002, 87:884–886.
Strupp C, Germing U, Scherer A, et al.: Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia 2002, 16:1–6.
Moreno-Aspitia A, Geyer S, Li C-Y, et al.: Multicenter phase II trial of thalidomide (thal) in adult patients with myelodysplastic syndromes (MDS) [abstract]. Blood 2002, 100:Abstract N998B.
List A, Tate W, Glinsmann-Gibson B: The immunomodulatory thalidomide analog, CC-5013, inhibits trophic response in VEGF in AML cells by abolishing cytokineinduced PI3 kinase/Akt activation [abstract]. Blood 2002, 100:139.
List A, Kurtin S, Roe DJ, et al.: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005, 352:11–19. The study that demonstrates the remarkable efficacy of lenalidomide in early MDS, and particularly in patients with deletion of 5q31.1.