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Evidence summaries

Melphalan and Prednisolone Plus Thalidomide Compared to other Treatments for Multiple Myeloma in the Elderly

Melphalan and prednisolone plus thalidomide is more effective than melphalan and prednisolone alone, and appears to be more effective than reduced-intensity stem cell transplantation using melphalan in improving overall and disease-free survival in newly diagnosed patients with multiple myeloma. Level of evidence: "A"

In a trial 1 447 patients aged 65-75 years with previously untreated myeloma were randomly assigned to receive either melphalan and prednisolone (MP) or melphalan and prednisolone plus thalidomide (MPT) or reduced-intensity stem cell transplantation usimg melphalan (MEL100). After a median follow-up of 51.5 months, median overall survival times were 33.2 months for MP, 51.6 months for MPT, and 38.3 months for MEL100, hazard ratio for overall survival favoring MPT 0.57 (95% CI 0.46 to 0.81, p=0.0006) against MP and 0,69 (95% CI 0.49 to 0.96, p=0.027) against MEL100. Relative improvement of disease-free survival was of similar magnitude. Deaths due to toxicity occurred in 4 patients in the MP, 6 patients in the MEL100, and no patients in the MPT group. Thrombosis or pulmonary embolism occurred in 12 patients (12%) treated with MPT. Neurotoxicity related to thalidomide was noted in more than half of the patients.

In another RCT 2 in newly diagnosed patients aged 65-85 years, MTP improved 2-year event-free survival (54% vs 27%), but did not significantly improve 3-year overall survival (80% vs 64%) compared with MP.

Comment: The risk of thromboembolism associated with thalidomide can be reduced by thromboprophylaxis, and the disability associated with neurotoxicity can be reduced by stopping the drug when moderately severe symptoms of neurotoxicity appear.

    References

    • Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, Renaud M, Harousseau JL, Guillerm G, Chaleteix C, Dib M, Voillat L, Maisonneuve H, Troncy J, Dorvaux V, Monconduit M, Martin C, Casassus P, Jaubert J, Jardel H, Doyen C, Kolb B, Anglaret B, Grosbois B, Yakoub-Agha I, Mathiot C, Avet-Loiseau H, Intergroupe Francophone du Myélome. 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 Oct 6;370(9594):1209-18. [PubMed]
    • Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M, Italian Multiple Myeloma Network, GIMEMA. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006 Mar 11;367(9513):825-31. [PubMed]

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