MRD-driven multiple myeloma treatment: next step forward

Published on July 30, 2020   37 min

Other Talks in the Category: Cell Biology

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Hi, I'm Ola Landgren. I'm Chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center and Professor of Medicine at Weill Cornell Medical College in New York City. Today I will give a talk about MRD Driven Multiple Myeloma Treatment: Next Step Forward.
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These are my disclosures.
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I also would like to emphasize that a lot of the slides I will share with you today cover our experience and our strategies, and I'm well aware that there are other perspectives and I'm of course very respectful of those.
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Let's start with the question, why is MRD testing relevant in multiple myeloma? I think there are two major aspects to address here. Number 1, MRD negativity can be achieved in both newly diagnosed and relapsed or refractory patients with multiple myeloma. So it's in every stage of the disease. Also, number 2, MRD status is not only something you can find, it's also a strong predictor of clinical outcomes in multiple myeloma. I will share with you a couple of slides to illustrate a little bit further what I mean when I show these two bullets.
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Number 1, here we have selected treatment responses in newly diagnosed patients with myeloma, and I selected on the very left, one old study back from 2003 in the New England Journal of Medicine, using the old VAD regiment with one versus two transplants, then if you move to the right, you have the VRd or RVd regiment plus-minus transplant, this is the 2009 IFM study. Then you move to the right, you have the single-arm KRd without transplant. There's not yet any published study with comparison between KRd and other regiments. So for now, this is the only published paper with a single arm. Then we have the VMP plus-minus daratumumab, then we have on the very right, Rev/Dex plus-minus velcade also without transplant. As you see here, the three middle studies, they all include MRD testing. The left and the right study, they do not include that. If you look in further detail in the middle, you see that MRD status as expected ranges quite a lot, for example, the transplant arm on the VAD plus-minus transplant on the left goes as high as 79 percent and the RVd arm is 65 percent. If you move to the very right, again, you see that the Dara-VMP arm is 22 and the VMP arm is only six percent. There is some evidence of MRD negativity even in VMP. Then in the middle, you see 77 and 42 percent. If you look even closer, you see that the level of MRD negativity is different in these different studies. The study on the left reports 10 to minus four, which formally is really not MRD negativity. The definition by current criteria is 10 to minus five. They are saying here that one cell in 10,000 has been ruled out and then they declare that's true in 79 percent. But it should really be one cell in 100,000 if you follow guidelines, 10 to minus five. There is also emerging data that if you raise the bar 10 to minus six, so that's one cell in a million, that that could even be a stronger predictor for better progression-free survival. So I caution you when you look across these different studies.
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MRD-driven multiple myeloma treatment: next step forward

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