FACULTY COMMENTS

DR ORLOWSKI: Our Phase III trial compared bortezomib with or without pegylated liposomal doxorubicin (PLD) in patients with relapsed or refractory multiple myeloma.

The median time to progression, progression-free survival and 15-month survival rate are all significantly greater with the combination.

The overall response rate doesn’t appear much different between the two arms, partially because we have to report it in an intent-to-treat analysis as opposed to the response-evaluable population. Still, the response quality, as measured by CR and very good PR (VGPR), was about 30 percent with bortezomib and PLD versus 20 percent with bortezomib alone.

Also, we saw that there seemed to be a special benefit with this combination for patients with high-risk features, such as patients with both relapsed and refractory disease or patients with a moderate to high ß₂-microglobulin. Usually, trials show just the opposite — that it’s the good-risk patients that do the best. I can’t speculate as to why we saw this opposite effect.

DR LONIAL: This paper clearly established that while the overall response rate was not appreciably different, a much higher rate of VGPR or better was observed in the patients treated with PLD and bortezomib. This led to an improvement in time to progression and overall survival.

I believe this is a two-drug combination that improves overall survival compared to single-agent bortezomib. Based on this trial, you can feel confident that PLD with bortezomib will have a better response rate for a bortezomib-naïve patient.

DR JAKUBOWIAK: To Dr Orlowski’s credit, this was the first randomized study in patients with relapsed disease to show that a two-drug combination with a novel agent was superior to a novel single agent, which was bortezomib.