Abstract
8123 Background: Even in the era of gene expression profiling (GEP) providing superior risk discrimination, M-CA remains an independent adverse feature for overall survival (OS) and event-free survival (EFS). Here we examined whether the percentage of such M-CA (%M-CA) had additional prognostic implications. Methods: Among 1,324 patients enrolled in TT protocols, 441 (33%) had M-CA. The %M-CA was determined from the ratio of MM-typical M-CA and total metaphase count, typically 20. Analysis was done of OS and EFS, per protocol, according to tertiles of M-CA and in relationship to absence of M-CA. Results: We are confirming the superior outcome of absence of M-CA (OS; p<0.0001; EFS: p=0.02). Among those with M-CA, the 147 patients with low-tertile M-CA<15% fared better than the remainder with mid-tertile M-CA15%-<35% and top-tertile M-CA>35% (OS, EFS; both p<0.001). In TT1, only no M-CA stood out as being associated with superior OS and EFS (both p=0.003). For the control arm of TT2, there was a graded shortening of both outcomes with progressive M-CA% whereas, for TT2 plus thalidomide, only the top-tertile M-CA group had inferior OS/EFS (both p<0.001). With TT3, although overall further improved versus TT2+thalidomide, the major difference was between low- and mid-tertile groups (both p<0.0001). Considering all 1,324 patients including those without M-CA, M-CA>15% was the only surviving CA category affecting both OS and EFS adversely (p<0.001), also in the presence of GEP-defined high-risk available in 767 subjects, whereas TT2 and TT3 trials imparted significant OS and EFS benefit in comparison with TT1. Conclusions: While validating any M-CA as an adverse prognostic feature, only the high-tertile M-CA group survived the multivariate model, even in the presence of GEP-risk. Thus, %M-CA should be considered in prognostic models for MM. No significant financial relationships to disclose.
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