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ASCO 2013: Dr. Usmani - Total therapy 5 (TT5) for newly diagnosed high-risk multiple myeloma (HRMM): Comparison with predecessor trials total therapy 3a and 3b (TT3 a/b).

Saad Usmani, MD, FACP
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences
Little Rock, Arkansa, USA

06.03.13

Abstract Number: 
8539

Citation: 
J Clin Oncol 31, 2013 (suppl; abstr 8539)

Author(s): 
Saad Zafar Usmani, Sarah Waheed, Frits Van Rhee, Alan Mitchell, Alejandro Restrepo, Monica Grazziutti, John Crowley, Bart Barlogie; Myeloma Institute for Research and Therapy, Little Rock, AR; Cancer Research and Biostatistics, Seattle, WA

ABSTRACT: 

Background: HRMM has not benefited from advances achieved in the remainder 85% with low-risk MM. In order to guard against relapses during previous drug-free intervals in TT3, TT5 was designed as a dose-dense and less dose-intense program. Here we are reporting for the first time on the TT5 outcomes in comparison with TT3a/b results in HRMM. 

Methods: TT5 called for M-VTD-PACE induction with HPC collection. This was followed by tandem autologous stem cell transplants (ASCT) with hybrid regimens Mel80 plus VRD-PACE, sandwiched in between were 2 inter-transplant cycles of MEL20-VTD-PACE. Maintenance consisted of 3 years of alternating VRD and VMD (M, melphalan). As relapses were observed during maintenance, bortezomib was increased from 1.3mg/m2 to 1.5mg/m2 weekly. Results were compared with HRMM treated with TT3a/b (n=40/37). Data were compared with TT3 HRMM, involving 77 patients. Overall survival and progression free survival was analyzed employing Kaplan-Meier curves. Cox regression modeling was done for univariate and multivariate analyses. 

Results: Of 59 patients enrolled in TT5, CR was 66% including 10% with s-CR. The 18-mo OS was 92% v 74% with TT3 (p=0.009), whereas PFS was similar at 67% and 69%, respectively. A newly developed GEP-5 model distinguished 8 patients with a 36-mo OS estimate of 20% versus almost 90% for the remainder (p=0.04). On multivariate analysis that included TT5 and TT3, our GEP80 low-risk score, TT5 (vs TT3) and age <65yr were independent features linked to superior OS. 

Conclusions: This isthe first report of a dose-dense chemotherapeutic approach for newly diagnosed HRMM, which also introduced a hybrid Mel80-VRDPACE hybrid preparative regimen for ASCT. TT5 represents an advance in the management of GEP70-defined HRMM compared to predecessor trials TT3a/b for similar patients, with significant improvement in overall survival and tolerability compared with TT3 a/b. 

Clinical trial information: NCT00081939, NCT00572169, NCT00869232.


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ASCO 2013: Dr. Usmani - Total therapy 5 (TT5) for newly diagnosed high-risk multiple myeloma (HRMM): Comparison with predecessor trials total therapy 3a and 3b (TT3 a/b).

Saad Usmani, MD, FACP
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Sagar Lonial, MD
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Transplant
ASCO 2013: Dr. Usmani - Total therapy 5 (TT5) for newly diagnosed high-risk multiple myeloma (HRMM): Comparison with predecessor trials total therapy 3a and 3b (TT3 a/b).

Saad Usmani, MD, FACP
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences
Little Rock, Arkansa, USA


ASCO 2013: Dr. Nooka- Early versus delayed autologous stem cell transplant (ASCT) in patients receiving induction therapy with lenalidomide, bortezomib, and dexamethasone (RVD) for newly diagnosed multiple myeloma (MM).

Ajay Nooka, MD, MPH, FACP
Winship Cancer Institute of Emory University
Atlanta, Georgia, USA


ASCO 2013: Dr. Palumbo - Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed multiple myeloma (MM) patients.

Antonio Palumbio, MD
University Of Turin
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Noopur Raje, MD
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