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
- 27 May 2010
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 115 (21), 4168-4173
- https://doi.org/10.1182/blood-2009-11-255620
Abstract
The Total Therapy 3 trial 2003-33 enrolled 303 newly diagnosed multiple myeloma patients and was noted to provide superior clinical outcomes compared with predecessor trial Total Therapy 2, especially in gene expression profiling (GEP)–defined low-risk disease. We report here on the results of successor trial 2006-66 with 177 patients, using bortezomib, lenalidomide, and dexamethasone maintenance for 3 years versus bortezomib, thalidomide, and dexamethasone in year 1 and thalidomide/dexamethasone in years 2 and 3 in the 2003-33 protocol. Overall survival (OS) and event-free survival (EFS) plots were super-imposable for the 2 trials, as were onset of complete response and complete response duration (CRD), regardless of GEP risk. GEP-defined high-risk designation, pertinent to 17% of patients, imparted inferior OS, EFS, and CRD in both protocols and, on multivariate analysis, was the sole adverse feature affecting OS, EFS, and CRD. Mathematical modeling of CRD in low-risk myeloma predicted a 55% cure fraction (P < .001). Despite more rapid onset and higher rate of CR than in other molecular subgroups, CRD was inferior in CCND1 without CD20 myeloma, resembling outcomes in MAF/MAFB and proliferation entities. The robustness of the GEP risk model should be exploited in clinical trials aimed at improving the notoriously poor outcome in high-risk disease.Keywords
This publication has 18 references indexed in Scilit:
- TP53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3British Journal of Haematology, 2009
- Complete remission in multiple myeloma examined as time-dependent variable in terms of both onset and duration in Total Therapy protocolsBlood, 2009
- An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myelomaBlood, 2008
- Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2British Journal of Haematology, 2008
- High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosisPublished by American Society of Hematology ,2007
- A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1Blood, 2006
- The molecular classification of multiple myelomaBlood, 2006
- International uniform response criteria for multiple myelomaLeukemia, 2006
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958