Original article
Vol. 141 No. 2122 (2011)
Validation of prognostic factors and survival of patients with multiple myeloma in a real-life autologous stem cell transplantation setting: a Swiss single centre experience
- P Samaras
- M Blickenstorfer
- SR Haile
- D Siciliano
- U Petrausch
- A Mischo
- M Zweifel
- H Honegger
- U Schanz
- G Stüssi
- S Bauer
- A Knuth
- F Stenner-Liewen
Summary
PRINCIPLES: High-dose chemotherapy with subsequent autologous stem cell transplantation (ASCT) is an important treatment option in younger patients with multiple myeloma (MM). We analysed the outcome of patients treated at our institution outside the clinical trials framework and tried to identify risk factors prognostic for survival.
METHODS: Medical histories of the patients were screened for response, event-free survival (EFS) and overall survival (OS). Pre-transplant variables were analysed to identify possible prognostic risk factors.
RESULTS: Overall, 182 ASCT were performed in 120 patients with MM from 2002 to 2007. Treatment-related mortality (TRM) was 0.5%. Median EFS was 23.1 months (95% confidence interval [CI]: 19.4–28.4) and median OS was 49.8 months (95%CI: 43.7–not reached) in the whole patient population. The median OS in patients who received one ASCT was 46.4 months (95%CI: 35.2–not reached), and 63.7 months (95%CI: 48.9–not reached) in patients who underwent double ASCT.
Patients who already achieved a complete remission (CR) before ASCT had a longer EFS (p = 0.016) than patients without CR. Additionally, patients who achieved a CR after ASCT had a longer EFS (p = 0.0061) and OS (p = 0.0024) than patients without CR. ISS stage <III at first diagnosis strongly correlated with improved EFS (p = 0.0006) and OS (p <0.0001).
CONCLUSIONS: ASCT is a safe and effective treatment mode in eligible patients with MM. TRM was below average at our institution. Achievement of CR after transplantation was the most valuable predictor for improved overall survival.
References
- Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe francais du myelome. N Engl J Med. 1996;335:91–7.
- Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: Up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998;92:3131–6.
- Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875–83.
- Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006;354:1021–30.
- Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349:2495–502.
- Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007;25:2434–41.
- Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (vad) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005;106:35–9.
- Rajkumar SV, Rosinol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008;26:2171–7.
- Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: Results of an ifm phase ii study. Haematologica. 2006;91:1498–505.
- Popat R, Oakervee HE, Hallam S, Curry N, Odeh L, Foot N, et al. Bortezomib, doxorubicin and dexamethasone (pad) front-line treatment of multiple myeloma: Updated results after long-term follow-up. Br J Haematol. 2008;141:512–6.
- Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K, Pineda-Roman M, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: Early results of total therapy 3. Br J Haematol. 2007;138:176–85.
- Nair B, van Rhee F, Shaughnessy JD, Jr., Anaissie E, Szymonifka J, Hoering A, et al. Superior results of total therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with vrd maintenance. Blood. 2010;115:4168–73.
- Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E. Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood. 2010;115:3655–63.
- Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356:1110–20.
- Rowan K. Researchers debate best use of stem cell transplants in patients with multiple myeloma. J Natl Cancer Inst. 2009;101:1608–11.
- Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.
- Kroger N, Schwerdtfeger R, Kiehl M, Sayer HG, Renges H, Zabelina T, et al. Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma. Blood. 2002;100:755–60.
- Jost LM, Honegger HP, Stahel RA. high-dose chemotherapy with autologous bone marrow transplantation: 11 years’ experience in Zurich. Schweiz Med Wochenschr. 2000;130:60–9.
- Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.
- Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Statist Assoc. 1958;53:457–81.
- Cox DR. Regression models and life tables (with discussion). J R Statist Soc B. 1972;34:187–220.
- R development core team. R: A language and environment for statistical computing. R foundation for statistical computing, Vienna, Austria. Isbn 3-900051-07-0, url http://www.R-project.Org. 2009
- Jantunen E, Itala M, Lehtinen T, Kuittinen O, Koivunen E, Leppa S, et al. Early treatment-related mortality in adult autologous stem cell transplant recipients: A nation-wide survey of 1482 transplanted patients. Eur J Haematol. 2006;76:245–50.
- O’Shea D, Giles C, Terpos E, Perz J, Politou M, Sana V, et al. Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: A single-centre experience in 211 patients. Bone Marrow Transplant. 2006;37:731–7.
- Majolino I, Vignetti M, Meloni G, Vegna ML, Scime R, Tringali S, et al. Autologous transplantation in multiple myeloma: A gitmo retrospective analysis on 290 patients. Gruppo italiano trapianti di midollo osseo. Haematologica. 1999;84:844–52.
- Alegre A, Diaz-Mediavilla J, San-Miguel J, Martinez R, Garcia Larana J, Sureda A, et al. Autologous peripheral blood stem cell transplantation for multiple myeloma: A report of 259 cases from the Spanish registry. Spanish registry for transplant in mm (grupo espanol de trasplante hematopoyetico-geth) and pethema. Bone Marrow Transplant. 1998;21:133–40.
- Lahuerta JJ, Mateos MV, Martinez-Lopez J, Rosinol L, Sureda A, de la Rubia J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: Sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol. 2008;26:5775–82.
- Harousseau JL, Avet-Loiseau H, Attal M, Charbonnel C, Garban F, Hulin C, et al. Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: Long-term analysis of the ifm 99-02 and 99-04 trials. J Clin Oncol. 2009;27:5720–6.
- Badros A, Barlogie B, Siegel E, Morris C, Desikan R, Zangari M, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol. 2001;114:600–7.
- Cuzick J, Cooper EH, MacLennan IC. The prognostic value of serum beta 2 microglobulin compared with other presentation features in myelomatosis. Br J Cancer. 1985;52:1–6.
- Jagannath S, Barlogie B, Dicke K, Alexanian R, Zagars G, Cheson B, et al. Autologous bone marrow transplantation in multiple myeloma: Identification of prognostic factors. Blood. 1990;76:1860–6.
- Vesole DH, Barlogie B, Jagannath S, Cheson B, Tricot G, Alexanian R, Crowley J. High-dose therapy for refractory multiple myeloma: Improved prognosis with better supportive care and double transplants. Blood. 1994;84:950–6.
- Harousseau JL, Attal M, Divine M, Marit G, Leblond V, Stoppa AM, et al. Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: A report of the French registry on autologous transplantation in multiple myeloma. Blood. 1995;85:3077–85.