Abstract 531

Introduction:

TT3-I imparted high CR rates and superior overall survival (OS) and event-free survival (EFS). Bortezomib pharmaco-genomic studies, performed concurrently, revealed that gene expression profiling (GEP) changes 48hr after a bortezomib test-dose had major prognostic significance, which we wished to validate in TT3-S. The purpose of this work is to compare clinical outcomes among the 303 TT3-I and 177 TT3-S patients.

Methods:

Our MM data base was scrutinized for patient characteristics and outcomes of the 2 cohorts in terms of CR rates and duration, as well as OS and EFS, in the context of major prognostic variables (cytogenetic abnormalities (CA), B2M, LDH, GEP risk).

Results:

Patients in the 2 studies were comparable except for a higher incidence of several adverse features in TT3-S: albumin <3.5g/dL in 45% v 25% (p<0.001), B2M >=3.5mg/L in 57% v 45% (p=0.012) and GEP-defined high-risk in 22% v 15% (p=0.035). Outcome comparisons for TT3-S v TT3-I were almost identical: 3-year estimates of OS 80% v 82%, EFS 81% v 77%, sustained CR 61% v 62%; in GEP low-risk/no CA subgroup: OS 94% v 91%, EFS 90% v 87%, sustained CR 98% v 94% (Figure 1a); GEP low-risk/CA subgroup: OS 81% v 79%, EFS 81% v 74%, sustained CR 86% v 90%; GEP high-risk/no CA subgroup: OS 70% v 82%, EFS 75% v 46%, sustained CR 75% v 30%; GEP high-risk/CA subgroup: OS 48% v 41%, EFS 52% v 38%, sustained CR 60% v 55% (Figure 1b). None of the Kaplan-Meier plots for these GEP-risk/CA constellations were different between TT3-S and TT3-I.

Figure 1:
Figure 1:. CR Duration from onset of CR . / a) GEP low-risk/no CA subgroup: b) GEP high-risk/no CA subgroup:
View largeDownload slide

CR Duration from onset of CR

a) GEP low-risk/no CA subgroup: b) GEP high-risk/no CA subgroup:

Figure 1:
Figure 1:. CR Duration from onset of CR . / a) GEP low-risk/no CA subgroup: b) GEP high-risk/no CA subgroup:
View largeDownload slide

CR Duration from onset of CR

a) GEP low-risk/no CA subgroup: b) GEP high-risk/no CA subgroup:

Close modal
Conclusions:

We have validated the remarkable success of the TT3 principle in low-risk MM, whereas high-risk disease deserves novel strategies as being pursued in TT5 with dose-dense and less dose-intense therapies.

Disclosures:

van Rhee:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Topics:
albumins, bortezomib, chromosome abnormality, databases, gene expression profiling, multiple myeloma, test dose, treatment outcome, disclosure, genome

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
Sign in via your Institution