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Randomized Controlled Trial
. 2008 Mar;140(6):625-34.
doi: 10.1111/j.1365-2141.2007.06921.x.

Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2

Mauricio Pineda-Roman  1 , Maurizio Zangari, Jeff Haessler, Elias Anaissie, Guido Tricot, Frits van Rhee, John Crowley, John D Shaughnessy Jr, Bart Barlogie
Affiliations
Randomized Controlled Trial

Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2

Mauricio Pineda-Roman et al. Br J Haematol. 2008 Mar.

Abstract

Total therapy 3 (TT3), incorporating bortezomib up-front into a tandem transplant regimen for newly diagnosed multiple myeloma (MM), effected 2-year complete response (CR) estimates >90%, which appeared superior to results reported for total therapy 2 (TT2). With median follow-up times of 2 years with TT3 and 5 years with TT2, the clinical outcomes of 303 patients in the former and 668 in the latter trial were compared, including the subset of 607 patients with gene expression profiling (GEP) data. With similar baseline prognostic factors, event-free survival (EFS) (P = 0.0002) and CR duration (P = 0.003) were superior with TT3 vs. TT2 with a strong trend noted also for improved overall survival (OS) (P = 0.16). In the GEP-defined FGFR3 subgroup, TT3 imparted significantly superior OS, EFS and CR duration vis-à-vis TT2. Matching 300 patients each by standard prognostic factors, TT3 yielded superior EFS and CR duration and borderline superior OS. The advantage of TT3 still pertained when the comparison was limited to patients who completed TT2 consolidation rapidly within 24 months. Our data strongly suggest that the addition of bortezomib in TT3 was accountable for its superior performance rather than greater compliance with protocol completion as a result of greater dose-density in TT3 vs. TT2.

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Figures

Fig 1
Fig 1
Treatment schema for TT2 and TT3.
Fig 2
Fig 2
Progression of patients through TT3 and TT2.
Fig 3
Fig 3
(A) Cumulative complete response rates with TT3 and TT2 by treatment arm. (B) Complete response duration. (C) Event-free survival. (D) Overall survival.
Fig 4
Fig 4
Time from protocol steps to event in TT3 and TT2.
Fig 5
Fig 5
(A) Duration of complete remission from its onset according to gene expression profiling (GEP)-defined risk. (B) Event-free survival from treatment start according to GEP-defined risk. (C) Overall survival from treatment start according to GEP-defined risk. (D) Duration of complete remission from its onset in GEP-defined FGFR3/MMSET subgroup. (E) Event-free survival in GEP-defined FGFR3/MMSET subgroup. (F) Overall survival in GEP-defined FGFR3/MMSET subgroup.
Fig 6
Fig 6
Clinical outcomes by protocol for those who entered maintenance within 2 years of study entry. (A) Event-free survival. (B) Overall survival.
Fig. 7
Fig. 7
Pair-mate analysis for patients enrolled in TT3 and TT2 protocols. (A) Complete remission duration comparison among patients matched on standard prognostic factors [cytogenetic abnormalities (CA), LDH, B2M, albumin – using categorical cut-offs applied in Table III]. (B) Event-free survival comparison among patients matched on standard prognostic factors [cytogenetic abnormalities (CA), LDH, B2M, albumin – using categorical cut-offs applied in Table II]. (C) Overall survival comparison among patients matched on standard prognostic factors [cytogenetic abnormalities (CA), LDH, B2M, albumin – using categorical cut-offs applied in Table II].
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