Abstract
Multiple myeloma (MM) survival plots usually display steeper initial and shallower subsequent slopes reflecting differences in disease biology and likely prognostic factors (PF). S9321 trial was selected to determine PF operative at baseline and subsequent 3, 4, 5, and 7-year landmarks (LM-0, LM-3, LM-4, LM-5, and LM-7). With a median follow-up of 8.2 years, survival was similar in transplant and standard therapy arms, justifying data pooling. Median survival for 775 eligible patients is 48 months. According to proportional hazards models, seven of 12 investigated baseline variables retained independent significance for LM-0, of which only two (beta-2-microglobulin and age) extended out to LM-7; the remaining five comprised features of disease aggressiveness (lactate dehydrogenase, calcium, platelet count, C-reactive protein) and host co-morbidity (performance status). Our observations of LM dependency of PF can be exploited toward advancing myeloma therapy by stratifying patients according to whether early or late portions of the survival history are being targeted.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
van Rhee F, Anaissie E, Angtuaco E et al (2010) Chapter 109. Myeloma. In: Kaushansky K (ed) Williams hematology, 8th edn. McGraw-Hill, New York (in press)
Kyle R, Rajkumar SV (2004) Multiple myeloma. N Engl J Med 351:1860–1873
Greipp PR, San Miguel J, Durie BGM et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:1–9
Durie BGM, Salmon SE (1975) A clinical system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer 36:842–854
Attal M, Harousseau JL, Facon T et al (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502
Child JA, Morgan GJ, Davies FE et al (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875–1883
Cavo M, Tosi P, Zamagni E et al (2007) Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. JCO 25:2434–2441
Barlogie B, Tricot G, Rasmussen E et al (2006) Thalidomide and hematopoietic-cell transplantation for multiple. N Engl J Med 354:1021–1030
Nair B, van Rhee F, Shaughnessy JD et al (2010) Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with bortezomib, lenalidomide and dexamethasone (VRD) maintenance. Blood 115:4168–4173. doi:10.1182/blood-2009-11-255620
Singhal S, Mehta J, Desikan R et al (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341:1565–1571
Richardson PG, Blood E, Mitsiades C et al (2006) A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108:3458–3464
Palumbo A, Bringhen S, Liberati A et al (2008) Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 112:3107–3114
Rajkumar SV, Jacobus S, Callander N et al (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomized controlled trial. Lancet Oncol 11:29–37
San Miguel JF, Schlag R, Khuagena NK et al (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 356:906–917
Barlogie B, Kyle RA, Anderson KC et al (2006) Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US intergroup trial S9321. JCO 24:929–936
Barlogie B, Attal M, Crowley J et al (2010) Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group and University of Arkansas for Medical Sciences. JCO 28:1209–1214
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
Cox DR (1972) Regression models and life tables. J R Stat Soc B 34:187–202
Han G, Schell MJ, Kim J (2010) Improved survival modeling using a reduced piecewise exponential approach. J Am Stat Assoc (in press)
Mueller HG, Wang JL (1994) Hazard rate estimation under random censoring with varying kernels and bandwidths. Biometrics 50:61–76
Acknowledgment
This study was supported in part by the following PHS Cooperative Agreement grant awarded by the National Cancer Institute, DHHS to the Southwest Oncology Group: CA38926.
Financial disclosures
None
Author information
Authors and Affiliations
Corresponding author
Additional information
Multiple myeloma survival plots usually display steeper initial and shallower subsequent slopes, reflecting differences in disease biology, which in turn may be governed by different baseline prognostic factors. Applying serial landmark techniques to 775 newly diagnosed patients enrolled in SWOG trial S9321 with a median follow-up of more than 8 years, LDH and calcium governed the early survival phase, while B2M was the sole feature that retained independent significance for later survival from 3, 4, 5, and 7-year landmarks.
Rights and permissions
About this article
Cite this article
Barlogie, B., Bolejack, V., Schell, M. et al. Prognostic factor analyses of myeloma survival with intergroup trial S9321 (INT 0141): examining whether different variables govern different time segments of survival. Ann Hematol 90, 423–428 (2011). https://doi.org/10.1007/s00277-010-1130-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-010-1130-y