Table 3

Results of multivariate analysis of the effect (losses only or total) of genomic complexity on TTFT or TTST estimates for previously untreated or previously treated CLL patients

Risk factorPreviously untreated patients (TTFT)
Previously treated patients (TTST)
Hazard ratioSignificance valueHazard ratioSignificance value
Genomic complexity (losses)     
    IgVH (98%) status unmutated 3.64 0.01 2.58 0.09 
    ZAP-70 positive 4.81 <0.01 1.85 0.34 
    Rai stage 1 or 2 versus 0 6.97 <0.01 NA — 
    CD38 (30%) positive 0.78 0.54 1.25 0.65 
    del17p/del11q present 0.34 0.13 1.01 0.99 
    p53 exon 5-9 mutations 0.7 0.64 2.06 0.31 
    Genomic complexity (losses) 9.95 0.01 2.82 0.02 
Genomic complexity (total)     
    IgVH (98%) status unmutated 4.19 <0.01 2.58 0.09 
    ZAP-70 positive 4.17 <0.01 1.85 0.34 
    Rai stage 1 or 2 versus 0 5.73 <0.01 NA — 
    CD38 (30%) positive 0.77 0.51 1.25 0.65 
    del17p/del11q present 0.35 0.13 1.01 0.99 
    p53 exon 5-9 mutations 1.79 0.36 2.06 0.31 
    Genomic complexity (total) 3.28 0.04 2.82 0.02 
Risk factorPreviously untreated patients (TTFT)
Previously treated patients (TTST)
Hazard ratioSignificance valueHazard ratioSignificance value
Genomic complexity (losses)     
    IgVH (98%) status unmutated 3.64 0.01 2.58 0.09 
    ZAP-70 positive 4.81 <0.01 1.85 0.34 
    Rai stage 1 or 2 versus 0 6.97 <0.01 NA — 
    CD38 (30%) positive 0.78 0.54 1.25 0.65 
    del17p/del11q present 0.34 0.13 1.01 0.99 
    p53 exon 5-9 mutations 0.7 0.64 2.06 0.31 
    Genomic complexity (losses) 9.95 0.01 2.82 0.02 
Genomic complexity (total)     
    IgVH (98%) status unmutated 4.19 <0.01 2.58 0.09 
    ZAP-70 positive 4.17 <0.01 1.85 0.34 
    Rai stage 1 or 2 versus 0 5.73 <0.01 NA — 
    CD38 (30%) positive 0.77 0.51 1.25 0.65 
    del17p/del11q present 0.35 0.13 1.01 0.99 
    p53 exon 5-9 mutations 1.79 0.36 2.06 0.31 
    Genomic complexity (total) 3.28 0.04 2.82 0.02 

Multivariate analysis was performed using Cox proportional hazards models. Modeling was performed separately using the 139 first treatment events (for TTFT) or the 48 subsequent treatment events (for TTST). Models included either visual genomic complexity based on losses only (losses) or total visual complexity (total = losses + gains + UPD). TTFT analysis included as binary covariates ZAP-70+, IgVH status unmutated, Rai stage (coded as stage 1/2 vs 0), presence of either del11q or del17p, presence of p53 exon 5-9 mutations and CD38 expression in more than 30% of CD5+/CD19+ cells. The same factors except Rai stage were considered in the multivariate analysis of TTST. Models were interpreted based on the hazard ratio estimates for factors of interest and their P values.

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