Prognostic implications of cumulative dosing in total therapy 3

To the editor:

In response to requests from readers¹  we are providing additional analyses regarding whether taking patient size into account changes the conclusions from our paper in Blood.²  We performed time-dependent analyses of cumulative dosing of velcade, thalidomide, and dexamethasone (VTD) components with and without adjustment for baseline body surface area (BSA) both per date of publication and per follow-up as of April 20, 2012. Adjustments for BSA were performed by dividing the cumulative dose by BSA. These additional analyses allow a side-by-side comparison of the univariate models presented in our original publication²  with identical models adjusted for BSA, and clearly indicates that our conclusions regarding the importance of cumulative dosing stand, even when BSA is accounted for. Table 1 shows univariate analyses for overall survival and Table 2 for progression-free survival (PFS). Supplemental Tables 1, 2, and 3 (available on the Blood Web site; see the Supplemental Materials link at the top of the letter) present these data in the context of glucocorticoid receptor NR3C1 tertile expression levels.

It is important to note that these analyses using BSA adjustment are completely compatible with those previously published for bortezomib, as well as for dexamethasone and thalidomide. In each of these additional analyses, adjustment for BSA resulted in only minor changes to the hazard ratios. Therefore we believe the relationship between cumulative dosing and outcomes does not simply reflect impact of body size on outcomes.