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Multiple Myeloma: Upfront Therapy and Longer Remissions

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: Thursday, Jan 18, 2018



Transcript: 

Thomas G. Martin, MD: In regard to upfront therapy for patients, the NCCN has really come up with great guidelines on what regimens to use. There are preferred regimens for patients who are transplant eligible, and the most common one we use in the United States is probably RVD, or lenalidomide, bortezomib, and dexamethasone. That by far is probably our most frequently used regimen. But there are many others. Most of the time these days we’re using triplet-based regimens. Some of the other triplets are bortezomib, cyclophosphamide, and dexamethasone, or VCD; and carfilzomib, Revlimid [lenalidomide], and dexamethasone, or KRD; which has really shown to be quite a potent regimen and is currently in a randomized clinical trial. But it’s part of the preferred regimens for frontline therapy. There are also some doublets for transplant-eligible patients, like lenalidomide, or Revlimid, and dexamethasone; or bortezomib and dexamethasone. There are also some other ones that are used more commonly in Europe, like bortezomib, doxorubicin, and dexamethasone. Of those, the most common ones we use are probably RVD and VCD and KRD in the United States.

In newly diagnosed patients, we’ve really transformed initial therapy, especially in transplant-eligible patients, to using triplets versus doublets. We do that somewhat in the transplant-ineligible population, too. In a recent randomized study, the SWOG-0777 study, it really showed that we can get deeper remissions and even better overall survival in patients receiving up-front triple therapy or triplet therapy versus a doublet. In the SWOG study, they randomized patients who were transplant eligible or ineligible to receive lenalidomide, bortezomib, and dexamethasone, the standard RVD, to lenalidomide and dexamethasone, or RD. So, it was RVD versus RD.

What we found was that there was an advantage both in progression-free survival, a difference of 43 months with RVD versus 30 months with RD, and an improvement in overall survival, which is really amazing. The overall survival difference was quite large, almost 11 months: 75 months in overall survival versus 64 months for those receiving RD as frontline therapy.

In regard to the NCCN preferred regimens for the transplant-ineligible patients, it really depends on how robust that patient is. There are a variety of regimens that we can use on the list and we choose based on an individual patient. But the common ones are also similar to the transplant eligible setting. We have RVD: lenalidomide, bortezomib, and dexamethasone. We have the VCD: bortezomib, cyclophosphamide, and dexamethasone. But also, the doublets are perhaps used even more often in this population with bortezomib and dexamethasone, or lenalidomide and dexamethasone. There was also a large trial in Europe, which put on the list 2 other carfilzomib-based regimens: carfilzomib, Cytoxan [cyclophosphamide], and dexamethasone; and carfilzomib, Revlimid, and dexamethasone.

Gareth Morgan, MD, PhD: Traditionally, we’ve shown in the last year that triplets outperform doublets of therapy. And so, it becomes a very logical next step to use quadruplets. The issue is, what is the toxicity of a quadruplet compared to a triplet? Toxicity comes in 2 levels. One is physical toxicity, and the other is financial toxicity. At some level, the financial toxicity is what’s going to drive the use of these agents. And so, it’s likely they’ll be better, it’s likely they’ll be tolerated, and I actually believe the future is all about quadruplets. However, we’ll need to find a way of dealing with the cost of these drugs. You might use one triplet with one set of drugs, followed by a triplet with another set of drugs. But I think most physicians would rather use a quadruplet these days, if they could.

Transcript Edited for Clarity 
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Transcript: 

Thomas G. Martin, MD: In regard to upfront therapy for patients, the NCCN has really come up with great guidelines on what regimens to use. There are preferred regimens for patients who are transplant eligible, and the most common one we use in the United States is probably RVD, or lenalidomide, bortezomib, and dexamethasone. That by far is probably our most frequently used regimen. But there are many others. Most of the time these days we’re using triplet-based regimens. Some of the other triplets are bortezomib, cyclophosphamide, and dexamethasone, or VCD; and carfilzomib, Revlimid [lenalidomide], and dexamethasone, or KRD; which has really shown to be quite a potent regimen and is currently in a randomized clinical trial. But it’s part of the preferred regimens for frontline therapy. There are also some doublets for transplant-eligible patients, like lenalidomide, or Revlimid, and dexamethasone; or bortezomib and dexamethasone. There are also some other ones that are used more commonly in Europe, like bortezomib, doxorubicin, and dexamethasone. Of those, the most common ones we use are probably RVD and VCD and KRD in the United States.

In newly diagnosed patients, we’ve really transformed initial therapy, especially in transplant-eligible patients, to using triplets versus doublets. We do that somewhat in the transplant-ineligible population, too. In a recent randomized study, the SWOG-0777 study, it really showed that we can get deeper remissions and even better overall survival in patients receiving up-front triple therapy or triplet therapy versus a doublet. In the SWOG study, they randomized patients who were transplant eligible or ineligible to receive lenalidomide, bortezomib, and dexamethasone, the standard RVD, to lenalidomide and dexamethasone, or RD. So, it was RVD versus RD.

What we found was that there was an advantage both in progression-free survival, a difference of 43 months with RVD versus 30 months with RD, and an improvement in overall survival, which is really amazing. The overall survival difference was quite large, almost 11 months: 75 months in overall survival versus 64 months for those receiving RD as frontline therapy.

In regard to the NCCN preferred regimens for the transplant-ineligible patients, it really depends on how robust that patient is. There are a variety of regimens that we can use on the list and we choose based on an individual patient. But the common ones are also similar to the transplant eligible setting. We have RVD: lenalidomide, bortezomib, and dexamethasone. We have the VCD: bortezomib, cyclophosphamide, and dexamethasone. But also, the doublets are perhaps used even more often in this population with bortezomib and dexamethasone, or lenalidomide and dexamethasone. There was also a large trial in Europe, which put on the list 2 other carfilzomib-based regimens: carfilzomib, Cytoxan [cyclophosphamide], and dexamethasone; and carfilzomib, Revlimid, and dexamethasone.

Gareth Morgan, MD, PhD: Traditionally, we’ve shown in the last year that triplets outperform doublets of therapy. And so, it becomes a very logical next step to use quadruplets. The issue is, what is the toxicity of a quadruplet compared to a triplet? Toxicity comes in 2 levels. One is physical toxicity, and the other is financial toxicity. At some level, the financial toxicity is what’s going to drive the use of these agents. And so, it’s likely they’ll be better, it’s likely they’ll be tolerated, and I actually believe the future is all about quadruplets. However, we’ll need to find a way of dealing with the cost of these drugs. You might use one triplet with one set of drugs, followed by a triplet with another set of drugs. But I think most physicians would rather use a quadruplet these days, if they could.

Transcript Edited for Clarity 
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