Phase III Data for Relapsed/Refractory Myeloma

Panelists: John Leonard, MD, New York-Presbyterian/Weill Cornell Center for Lymphoma and Myeloma; C. Ola Landgren, MD, Memorial Sloan Kettering Cancer Center; Alexander Perl, MD, Perelman School of Medicine, University of Pennsylvania; Anas Younes, MD, Memorial Sloan Kettering Cancer Center


John Leonard, MD: So, then obviously, there are a lot of new drugs in myeloma. We’ve had recent approvals. Or relatively recent. I guess they’re getting a little older now because we have much more experience with these drugs. But there are a couple of randomized trials that have looked at relapsed patients with lenalidomide/dexamethasone, and either carfilzomib in a study led by Keith Stewart or using daratumumab in a study led by Dimopoulos. Again, these kinds of 2-drug versus 3-drug combinations. Your take on these?

C. Ola Landgren, MD: I think these are 2 very important clinical papers. They are updates on existing data, but they are very important because they are large randomized studies. So, the first, the Stewart study, that’s the ASPIRE trial that uses carfilzomib/Revlimid/dexamethasone versus Revlimid/dexamethasone. And this update at this ASH is showing that the overall survival is significantly better in the 3-drug combination. Previously, it was only for progression-free survival. Now, they show that the hazard ratio is 0.079, it’s a 21% reduced risk of death. And the median overall survival is 48 versus 40 months, so that’s very important.

I think for the daratumumab study, that’s also very important. That’s an update on the POLLUX trial that uses daratumumab/Revlimid/dexamethasone versus the same Revlimid/dexamethasone. They do not have overall survival data, but they have an extended follow-up. And I think the follow-up time goes this time up to 33 months, in the paper that also comes from The New England Journal of Medicine. I think myeloma, it bought probably many pages in The New England Journal of Medicine the past few years here; that means so many papers. That previously was 18 months, now it’s 33 months. And it holds up and none of the 2 arms have yet met the median for progression-free survival. So, I think that’s also a very interesting combination for sure.

John Leonard, MD: So, then we couldn’t end a discussion on lymphoid malignancies without talking about CAR-T cells. I have not followed the myeloma CAR-T cell area quite as closely, but coming and looking through the abstracts just at a high level, it seems like there are a lot of great data coming along, very exciting data, although admittedly early. Berdeja and colleagues presented some data on the BCMA as a target antigen and some clinical activity. Your thoughts on these data and where that will go?

C. Ola Landgren, MD: Berdeja is presenting on the bb2121 CAR-T cell. That is a BCMA-targeted CAR-T cell approach. And they show, in those cohorts about 50 million cells of these CAR-T cells, that you have patients who reach even complete responses, similar to what we heard from the other disease areas. The numbers are relatively small, the follow-up time is restricted. There is another presentation by the UPenn group, by Adam Cohen. There is a presentation by the Memorial Sloan Kettering Cancer Center group also with Eric Smith, and I think there will be others also. In fact, there are 5 ongoing clinical trials using different CAR-T cells targeting BCMA in myeloma at this time. So, they all show very similar findings, that the therapy seems to work if you go in higher doses. You run into cytokine release syndrome. The bb2121 has less of that reportedly, but numbers were small. There are some patients who have been followed for up to a year who persist in CR, but numbers were small. It’s early. It’s exciting, but we need to see more data.

Transcript Edited for Clarity 
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