FACULTY COMMENTS

DR RICHARDSON: It was exciting to see Dr San Miguel present the randomized Phase III VISTA trial at the 2007 ASH meeting.

A protocol-specified interim analysis showed that the combination with bortezomib and melphalan/prednisone was significantly superior to melphalan/prednisone alone for all of the efficacy endpoints, including time to progression, progressionfree survival, overall survival and time to next therapy.

The difference in complete response rate — 35 percent for the bortezomib-based arm versus five percent for the control arm — was striking.

CR rates of this order of magnitude for older patients who are not candidates for transplant are quite remarkable, in my opinion.

We at Dana-Farber were the lead enroller for the US, and our experience was that the responses to the combination were rapid and deep. Moreover, adverse cytogenetics and poor renal function had no impact on VMP efficacy overall.

In terms of the side-effect profile, cytopenias were seen in both arms, and the neuropathy rate was higher, as one would expect, with VMP. In the majority of cases, however, it was reversible using the dose-reduction algorithm that is now a standard with bortezomib-based therapy.

Interestingly, low rates of deep vein thrombosis were observed on both arms with this combination approach.

The clinical implication of these data is that bortezomib and melphalan/prednisone is now an important standard in the upfront setting for patients who are not candidates for high-dose therapy.