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Multiple Myeloma: Second Relapse and Beyond

Insights From: Rafael Fonseca, MD, Mayo Clinic; Gareth Morgan, MD, PhD, UAMS Myeloma Institute; Thomas G. Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Tuesday, Feb 13, 2018



Transcript: 

Rafael Fonseca, MD: In myelomas, our patients go through treatment. We want to maximize the duration of first-line therapy. In fact, if you look at optimal induction followed by stem cell transplant and then maintenance, you can start envisioning about 5 years on average of disease control. If you take one of these optimal regimens for the first relapse, which could be KRD or daratumumab/RD, we’re adding another 2 to 3 years. So, we’re talking about 7 to 8 years for initial therapy. Now, for that patient, they still have a good number of options. I would venture to say that we have to consider the comorbidities, the tolerance to the previous regimen, and also the goals of therapy at that point. There are some patients for whom intensive, aggressive therapy is still warranted. In fact, that may even take us all the way back to considering another stem cell transplant.

If I had a patient who went through a transplant and after several years, gets one of those regimens and gets a few other years, and then is facing again the possibility of a relapse—let’s say you have a patient who was treated with KRD and is now experiencing a relapse 2 or 3 years later, and the patient is fit—I may consider daratumumab, pomalidomide, and dexamethasone as a prelude to doing a second stem cell transplant. All those factors come into play as we decide on the next lines of therapy. Now, there may be a patient who’s quite frail where we may want to minimize the toxicity. We may want to allow them to spend more time with their families. But I would say the average myeloma patient who’s able to reach the second and third relapse lines of therapy should know that there’s a plethora of options still available to them.

Gareth Morgan, MD, PhD: Choosing treatment is an important part of the physician’s role in the management of myeloma. It seems to me that there are a number of thought processes that govern treatment, and some physicians say to approach frontline treatment with one triplet, first relapse with a different triplet with a different mechanism of action, and third-line with yet another triplet. They should always be different with different mechanisms.

But not all relapses are the same. That simple idea of “it’s just triplets” doesn’t necessarily work out for every patient. And so, if you’ve had a good response to a transplant, you can use a transplant again. If you’ve been treated with carfilzomib, you tolerated it well, and you’ve been in remission for 3 years, it’s just as likely that it will work if that disease relapses at presentation. So, I think you always have to consider the type of relapse and the type of disease, restage, aim for maximum response, and then aim to control the disease during remission by longer-term exposure. I think that’s the real clinical conundrum, not alternating triplets every 2 years.

Transcript Edited for Clarity 
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Transcript: 

Rafael Fonseca, MD: In myelomas, our patients go through treatment. We want to maximize the duration of first-line therapy. In fact, if you look at optimal induction followed by stem cell transplant and then maintenance, you can start envisioning about 5 years on average of disease control. If you take one of these optimal regimens for the first relapse, which could be KRD or daratumumab/RD, we’re adding another 2 to 3 years. So, we’re talking about 7 to 8 years for initial therapy. Now, for that patient, they still have a good number of options. I would venture to say that we have to consider the comorbidities, the tolerance to the previous regimen, and also the goals of therapy at that point. There are some patients for whom intensive, aggressive therapy is still warranted. In fact, that may even take us all the way back to considering another stem cell transplant.

If I had a patient who went through a transplant and after several years, gets one of those regimens and gets a few other years, and then is facing again the possibility of a relapse—let’s say you have a patient who was treated with KRD and is now experiencing a relapse 2 or 3 years later, and the patient is fit—I may consider daratumumab, pomalidomide, and dexamethasone as a prelude to doing a second stem cell transplant. All those factors come into play as we decide on the next lines of therapy. Now, there may be a patient who’s quite frail where we may want to minimize the toxicity. We may want to allow them to spend more time with their families. But I would say the average myeloma patient who’s able to reach the second and third relapse lines of therapy should know that there’s a plethora of options still available to them.

Gareth Morgan, MD, PhD: Choosing treatment is an important part of the physician’s role in the management of myeloma. It seems to me that there are a number of thought processes that govern treatment, and some physicians say to approach frontline treatment with one triplet, first relapse with a different triplet with a different mechanism of action, and third-line with yet another triplet. They should always be different with different mechanisms.

But not all relapses are the same. That simple idea of “it’s just triplets” doesn’t necessarily work out for every patient. And so, if you’ve had a good response to a transplant, you can use a transplant again. If you’ve been treated with carfilzomib, you tolerated it well, and you’ve been in remission for 3 years, it’s just as likely that it will work if that disease relapses at presentation. So, I think you always have to consider the type of relapse and the type of disease, restage, aim for maximum response, and then aim to control the disease during remission by longer-term exposure. I think that’s the real clinical conundrum, not alternating triplets every 2 years.

Transcript Edited for Clarity 
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