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Key Studies in Newly-Diagnosed Multiple 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
Published: Thursday, Dec 07, 2017



Transcript: 

John Leonard, MD: So, from the standpoint of newly-diagnosed patients, the audience knows that transplant is clearly an important part of myeloma therapy. There are data looking at it. I know the IFM has some new studies on minimal residual disease and using that as a tool in the treatment of patients with myeloma. What are your thoughts on that study?

C. Ola Landgren, MD: Yes, so this is an update presented by Hervé Avet-Loiseau from the French group, and they have done very important work for very many years. And this is just another great study they have done. They actually published the first paper on the same population just a few months ago in The New England Journal of Medicine. And this study was designed to look at the combination of bortezomib with lenalidomide and dexamethasone after 3 cycles, transplant, 2 more cycles, and maintenance, versus giving 3 cycles, collect the cells and keep them in the freezer, and do 5 more cycles of the same therapy, and then maintenance. So, they were looking at the use of transplant up front versus keeping it and using it as rescue.

And the primary endpoint in that study was to look to see 3 years out, is there a difference in progression-free survival? The answer is yes, and the winner was transplant. So, when this was initially presented at ASH, I think that half the people who listened to it heard that transplant won. Although that was the winner, the people who heard that transplant lost were the people who went to the second presentation by the same group. Because what they had done is they stratified the data by response in the 2 arms, and they had preliminary data at the time showing that MRD negativity was achieved in both arms, more people in the transplant arm than in the other arm. But if you were MRD-negative, there was very similar progression-free survival. And that’s exactly what this new abstract is looking at, and now they have taken it to a new level. They have used sequencing-based data and not only flow cytometry data.

I think this abstract is important. It really pushes the field even more in the direction of what Anas was talking about before, what’s going to be the role for just throwing chemotherapy at every patient in the future. Is that really where we are going to go, or can we use markers to determine the use of that? I don’t pretend to know the answer to it, but I think the data here are very provocative and they suggest that maybe transplant could be given in patients where there is still detectable disease, and that’s what they suggest in the abstract.

John Leonard, MD: Great. Just 2 quick other points about transplant. There are 2 other studies. One on secondary malignancies, and one talking about lenalidomide maintenance both in transplant and non-transplant settings. Just the quick takeaways from that.

C. Ola Landgren, MD: The second paper or the first of those 2 you mentioned, the second malignancy paper, this is a large database that looks into patients in California. There were close to 16,000 patients, and they found 900 of them to develop a secondary malignancy. That was recognized many years ago in myeloma that there is an over risk for malignancy, particularly for hematologic malignancies. And the papers that came out in the 70s, they were accusing alkylators, and then for a while, people forgot about it and the therapies were not that good. And then when lenalidomide maintenance came into practice around 2010 or so, people started looking into it again and there was a signal. This study looks into patients treated with and without a transplant upfront, and they look at 5 and 10 years accumulative incidence of secondary malignancy. They show in the study that at 5 and 10 years of follow-up, the cumulative incidence of secondary malignancies are 4% versus 7% in the non-transplanted versus the transplanted patients. You basically double the rate of secondary malignancy in these patients, and they show that the particular increase is in the patients who are transplanted with regard to hematologic malignancy. So, they say maybe that’s another reason for thinking about other therapies.

Transcript Edited for Clarity 
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Transcript: 

John Leonard, MD: So, from the standpoint of newly-diagnosed patients, the audience knows that transplant is clearly an important part of myeloma therapy. There are data looking at it. I know the IFM has some new studies on minimal residual disease and using that as a tool in the treatment of patients with myeloma. What are your thoughts on that study?

C. Ola Landgren, MD: Yes, so this is an update presented by Hervé Avet-Loiseau from the French group, and they have done very important work for very many years. And this is just another great study they have done. They actually published the first paper on the same population just a few months ago in The New England Journal of Medicine. And this study was designed to look at the combination of bortezomib with lenalidomide and dexamethasone after 3 cycles, transplant, 2 more cycles, and maintenance, versus giving 3 cycles, collect the cells and keep them in the freezer, and do 5 more cycles of the same therapy, and then maintenance. So, they were looking at the use of transplant up front versus keeping it and using it as rescue.

And the primary endpoint in that study was to look to see 3 years out, is there a difference in progression-free survival? The answer is yes, and the winner was transplant. So, when this was initially presented at ASH, I think that half the people who listened to it heard that transplant won. Although that was the winner, the people who heard that transplant lost were the people who went to the second presentation by the same group. Because what they had done is they stratified the data by response in the 2 arms, and they had preliminary data at the time showing that MRD negativity was achieved in both arms, more people in the transplant arm than in the other arm. But if you were MRD-negative, there was very similar progression-free survival. And that’s exactly what this new abstract is looking at, and now they have taken it to a new level. They have used sequencing-based data and not only flow cytometry data.

I think this abstract is important. It really pushes the field even more in the direction of what Anas was talking about before, what’s going to be the role for just throwing chemotherapy at every patient in the future. Is that really where we are going to go, or can we use markers to determine the use of that? I don’t pretend to know the answer to it, but I think the data here are very provocative and they suggest that maybe transplant could be given in patients where there is still detectable disease, and that’s what they suggest in the abstract.

John Leonard, MD: Great. Just 2 quick other points about transplant. There are 2 other studies. One on secondary malignancies, and one talking about lenalidomide maintenance both in transplant and non-transplant settings. Just the quick takeaways from that.

C. Ola Landgren, MD: The second paper or the first of those 2 you mentioned, the second malignancy paper, this is a large database that looks into patients in California. There were close to 16,000 patients, and they found 900 of them to develop a secondary malignancy. That was recognized many years ago in myeloma that there is an over risk for malignancy, particularly for hematologic malignancies. And the papers that came out in the 70s, they were accusing alkylators, and then for a while, people forgot about it and the therapies were not that good. And then when lenalidomide maintenance came into practice around 2010 or so, people started looking into it again and there was a signal. This study looks into patients treated with and without a transplant upfront, and they look at 5 and 10 years accumulative incidence of secondary malignancy. They show in the study that at 5 and 10 years of follow-up, the cumulative incidence of secondary malignancies are 4% versus 7% in the non-transplanted versus the transplanted patients. You basically double the rate of secondary malignancy in these patients, and they show that the particular increase is in the patients who are transplanted with regard to hematologic malignancy. So, they say maybe that’s another reason for thinking about other therapies.

Transcript Edited for Clarity 
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