Thalidomide-dexamethasone versus Interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study
Massimo Offidani
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorLaura Corvatta
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorClaudia Polloni
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorMaria-Novella Piersantelli
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorSilvia Gentili
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorPiero Galieni
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorGiuseppe Visani
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorFrancesco Alesiani
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMassimo Catarini
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMarino Brunori
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorArduino Samori
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMaurizio Burattini
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorRiccardo Centurioni
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMario Ferranti
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorLuciano Giuliodori
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMarco Candela
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorAnna Mele
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMonica Marconi
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorPietro Leoni
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorMassimo Offidani
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorLaura Corvatta
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorClaudia Polloni
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorMaria-Novella Piersantelli
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorSilvia Gentili
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorPiero Galieni
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorGiuseppe Visani
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorFrancesco Alesiani
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMassimo Catarini
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMarino Brunori
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorArduino Samori
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMaurizio Burattini
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorRiccardo Centurioni
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMario Ferranti
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorLuciano Giuliodori
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMarco Candela
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorAnna Mele
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorMonica Marconi
Marche Multiple Myeloma Network, GEMaMM, Ancona, Italy
Search for more papers by this authorPietro Leoni
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona
Search for more papers by this authorSummary
Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive α-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P = 0·024) and overall survival (84% vs. 68%; P = 0·030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm (P = 0·014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.
References
- Abdelkefi, A., Ladeb, S., Torjman, L., Othman, T.B., Lakhal, A., Romdhane, N.B., Omri, H.E., Elloumi, M., Belaaj, H., Jeddi, R., Aissaoui, L., Ksouri, H., Hassen, A.B., Msadek, F., Saad, A., Hsairi, M., Boukef, K., Amouri, A., Louzir, H., Dellagi, K. & Abdeladhim, A.B. (2008) Single autologous stem-cell transplantationfollowed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood, 11, 1805–1810.
- Attal, M., Harousseau, J.L., Leyvraz, S., Doyen, C., Hu, C., Benboubker, L., Yacoub Agha, I., Bourhis, J.H., Garderet, L., Pegourie, B., Dumontet, C., Renaud, M., Voillat, L., Berthou, C., Marit, G., Monconduit, M., Caillot, D., Grobois, B., Avet-Louseau, H., Moreau, P. & Facon, T. (2006) Maintenance therapy with thalidomide improves survival in multiple myeloma patients. Blood, 108, 3289–3294.
- Barlogie, B., Tricot, G., Anaissie, E., Shaughnessy, J., Rasmussen, E., Van Rhee, F., Fassas, A., Zangari, M., Hollmig, K., Pineda-Roman, M., Lee, C., Talamo, G., Thertulien, R., Kiwan, E., Krishna, S., Fox, M. & Crowley, J. (2006) Thalidomide and hematopoietic-cell transplantation for multiple myeloma. New England Journal of Medicine, 354, 1021–1030.
- Brinker, B.T., Waller, E.K., Leong, T., Heffner, L.T. Jr, Redei, I., Langston, A.A. & Lonial, S. (2006) Maintenance therapy with thalidomide improves overall survival after autologous hematopoietic progenitor cell transplantation for multiple myeloma. Cancer, 106, 2171–2180.
- Cunningham, D., Powles, R., Malpas, J., Raje, N., Milan, S., Viner, C., Montes, A., Hicksh, T., Nicolson, M., Johnson, P., Treleaven, J., Raymond, J. & Gore, M. (1998) A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. British Journal of Haematology, 102, 495–502.
- Feyler, S., Rawstron, A., Jackson, G., Snowden, J.A., Cocks, K. & Johnson, R.J. (2007) Thalidomide maintenance following high-dose therapy in multiple myeloma: a UK myeloma forum phase II study. British Journal of Haematology, 139, 429–433.
- Fritz, E. & Ludwig, H. (2000) Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients. Annals of Oncology, 11, 1427–1436.
- Mihelic, R., Kaufman, J.L. & Lonial, S. (2007) Maintenance therapy in multiple myeloma. Leukemia, 21, 1150–1157.
- Offidani, M., Corvatta, L., Piersantelli, M.-N., Visani, G., Alesiani, F., Brunori, M., Galieni, P., Catarini, M., Burattini, M., Centurioni, R., Ferranti, M., Rupoli, S., Scortichini, A.R., Giuliodori, L., Candela, M., Capelli, D., Montanari, M., Olivieri, A., Poloni, A., Polloni, C., Marconi, M. & Leoni, P. (2006a) Thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood, 108, 2159–2164.
- Offidani, M., Corvatta, L., Marconi, M., Visani, G., Alesaini, F., Brunori, M., Galieni, P., Catarini, M., Burattini, M., Centurioni, R., Rupoli, S., Scortechini, A.R., Giuliodori, L., Candela, M., Capelli, D., Montanari, M., Olivieri, A., Piersantelli, M.-N. & Leoni, P. (2006b) Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenyter, phase II study. Haematologica, 91, 133–136.
- Sahebi, F., Spielberger, R., Kogut, N.M., Fung, H., Falk, P.M., Parker, P., Krishnan, A., Rodriguez, R., Nakamura, R., Nademanee, A., Popplewell, L., Frankel, P., Ruel, C., Tin, R., Ilieva, P., Forman, S.J. & Somio, G. (2006) Maintenance thalidomide following single cycle autologous peripheral blood stem cell transplant patients with multiple myeloma. Bone Marrow Transplantation, 37, 825–829.
- Salmon, S.E., Crowley, J.J., Balcerzak, S.P., Roach, R.W., Taylor, S.A., Rivkin, S.E. & Samlowski, W. (1998) Interferon versus interferon plus prednidone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study. Journal of Clinical Oncology, 16, 890–896.
- San-Miguel, J., Harousseau, J.L., Joshua, D. & Anderson, K.C. (2008) Individualizing treatment of patients with myeloma in the era of novel agents. Journal of Clinical Oncology, 26, 2761–2766.
- Spencer, A., Prince, H.M., Roberts, A., Bradstock, A. & Prosser, I. (2007) Thalidomide improves survival when used following ASCT. Haematologica, 92, 41.
- Stewart, A.K., Chen, C.I., Howson-Jan, K., White, D., Roy, J., Kovacs, M.J., Shustik, C., Sadura, A., Shepherd, L., Ding, K., Meyer, R.M. & Belch, A.R. (2004) Results of a multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplant. Clinical Cancer Research, 10, 8170–8176.
- The Myeloma Trialists’ Collaborative Group. (2001) Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. British Journal of Haematology, 113, 1020–1034.
- Yakoub-Agha, I., Doyen, C., Hulin, C., Marit, G., Voilat, L., Grosbois, B., Harosseau, J., Duguet, C., Zerbib, R., Facon, T. & Mary, J. (2006) A multicenter prospective randomized study testing non-inferiority of thalidomide 100 mg/day as compared with 400 mg/day in patients with refractory/relapsed multiple myeloma: result of a final analysis of the IFM 01-02 study. Journal of Clinical Oncology, 24, 7520.