Shorter Post-Relapse Survival (PRS) of Myeloma (MM) Patients Randomized to the Thalidomide (T) Arm of Total Therapy 2 (TT2) Related to Chromosome 1q21 Amplification (AMP1Q21, FISH) at Relapse

Autor: Guido Tricot, Bart Barlogie, Bart Burington, Joshua Epstein, John D. Shaughnessy, John Crowley, Teresa Milner, Maurizio Zangari, Ichiro Hanamura, Peter Stewart, Elias Anaissie, Klaus Hollmig, Erik Rasmussen, Frits van Rhee
Rok vydání: 2005
Předmět:
Zdroj: Blood. 106:1155-1155
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v106.11.1155.1155
Popis: Background: T2 randomized 668 patients up-front to +/− T as part of an intensive combination chemotherapy program prior to and after melphalan-based tandem autotransplants (Barlogie, ASCO 2005). Patients randomized to T had superior 2-yr CR (52% vs 43%, p Patients and Methods: All standard pre-treatment laboratory features including the frequency of cytogenetic abnormalities (CA) were similar in the 2 study arms. FISH data to assess amp1q21 were available for 475 patients at baseline and at relapse in 46 patients, of whom 30 also had baseline data. The amp1q21 index is a weighted average of the proportions of cells with 3 and >3 gene copies, ranging from 0 through 100. The post-relapse therapies were similar among the 2 arms and included T in all patients previously not on T and for most previously on T, often together with bortezomib + DEX (VTD regimen; Barlogie, Blood, 2004); DT-PACE and 3rd autotransplants as well as mini-allotransplants were also applied either as first or subsequent salvage maneuver - with similar frequencies among the 2 study arms. Results: The median PRS was 2.7 years among 95 patients (28%) in the no T group compared to 1.1 years for 67 patients (21%) on T (p=0.002). The amp1q21 index was similar in the 2 arms considering all 475 patients with FISH data available at diagnosis (p=0.28); this also applied for baseline levels among those who have relapsed (p=0.22). However, FISH analysis applied to 23 relapse samples from each arm showed that the 1q21 amp index was significantly higher in those on T than not on T (median, 69 vs 22; p Conclusion: Similar OS in the 2 study arms of TT2, despite higher CR rate and superior EFS on T, reflects the shorter PRS of T-randomized patients, which could be traced to differences in tumor genetics between the 2 arms: amp1q21 indices were similar at baseline but higher at relapse for patients on T; those not on T relapsed earlier; (3) among baseline and relapse variables examined, PRS was most strongly affected by amp1q21 index at relapse, neutralizing the notion of a potentially detrimental effect of initial treatment with T on subsequent salvage therapies.
Databáze: OpenAIRE
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