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Strategies for Upfront Therapy in Multiple Myeloma

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: Friday, Jan 19, 2018



Transcript: 

Rafael Fonseca, MD: When one thinks about how to approach a newly diagnosed patient, we still go through the exercise of deciding who would be a stem-cell transplant candidate versus who might not be, taking into consideration comorbidities. Now, a very important consideration there is that one does not want to undertreat older patients or patients who have comorbidities, yet at the same time you want to provide them with the right dose for their current situation.

               For a patient who’s fit and who’s going to go through a transplant, more often than not we would use a triplet combination. Nowadays, it’s usually a combination of bortezomib, lenalidomide, and dexamethasone. In some cases, particularly in patients with high-risk disease, we’re now considering the use of carfilzomib as part of that frontline combination, such as we would do with a KRD-like regimen. And then, of course, that would be followed with stem-cell transplant.

               Now for an elderly patient or a patient with comorbidities, since we’re not thinking necessarily about stem-cell transplant, we’re going to think about a triplet that would be used as an induction of consolidation. So for many of those patients, we would treat them with something like VRD—bortezomib, lenalidomide, and dexamethasone—and then transition to a maintenance approach. There are some patients who may not even tolerate that: very elderly patients, patients with other comorbidities who may be a candidate for a doublet only. But that’s really more of the exception. I would say most patients should be receiving a 3-drug based combination.

Thomas G. Martin, MD: There are some preferred regimens in terms of what I use in patients who have newly-diagnosed myeloma. For instance, in an elderly patient the first thing that I assess is, “How much therapy do I believe they’ll be able to tolerate?” and “What are their comorbidities?” In the elderly population, I often will start with a doublet-based therapy, either lenalidomide and dexamethasone or bortezomib and dexamethasone, and add a third drug.

For instance, I’ll start with Revlimid [lenalidomide] and dexamethasone and add bortezomib, so they would get RVD, a triplet. But I’ll do it in sequential ways, so that I can watch their toxicity very closely. The other thing is that comorbidities play a big role in what we select. With patients who have baseline neuropathy, we try to avoid medications like bortezomib, which may cause further neuropathy.

If the patient has significant renal insufficiency, sometimes we will avoid lenalidomide-based therapy and we’ll use bortezomib as the first regimen. Also, with some people who have diabetes or hypertension, blood pressure that’s out of control, I’ll avoid steroids. I’ll really dose reduce the dexamethasone in those patients. I really believe that, especially in the newly-diagnosed patient, it’s personalized medicine in the way we start medications, the way we continue medicines, and the way we dose adjust regimens as we treat them.

For frontline therapy for the unfit or the frail patients, there are regimens that we can use. There is an RVD-lite regimen where the lenalidomide, the bortezomib, and the dexamethasone are markedly dose reduced. It’s really trying to give the triplet-based therapy, but giving it in a way that the patient, especially this frail patient, is going to be able to tolerate it. There are a lot of dose reductions for many of the medications in the elderly and frail patients. And I would encourage everybody to look for those dose reductions—they’re online—prior to starting any therapy for almost all the myeloma medications.

Transcript Edited for Clarity 
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Transcript: 

Rafael Fonseca, MD: When one thinks about how to approach a newly diagnosed patient, we still go through the exercise of deciding who would be a stem-cell transplant candidate versus who might not be, taking into consideration comorbidities. Now, a very important consideration there is that one does not want to undertreat older patients or patients who have comorbidities, yet at the same time you want to provide them with the right dose for their current situation.

               For a patient who’s fit and who’s going to go through a transplant, more often than not we would use a triplet combination. Nowadays, it’s usually a combination of bortezomib, lenalidomide, and dexamethasone. In some cases, particularly in patients with high-risk disease, we’re now considering the use of carfilzomib as part of that frontline combination, such as we would do with a KRD-like regimen. And then, of course, that would be followed with stem-cell transplant.

               Now for an elderly patient or a patient with comorbidities, since we’re not thinking necessarily about stem-cell transplant, we’re going to think about a triplet that would be used as an induction of consolidation. So for many of those patients, we would treat them with something like VRD—bortezomib, lenalidomide, and dexamethasone—and then transition to a maintenance approach. There are some patients who may not even tolerate that: very elderly patients, patients with other comorbidities who may be a candidate for a doublet only. But that’s really more of the exception. I would say most patients should be receiving a 3-drug based combination.

Thomas G. Martin, MD: There are some preferred regimens in terms of what I use in patients who have newly-diagnosed myeloma. For instance, in an elderly patient the first thing that I assess is, “How much therapy do I believe they’ll be able to tolerate?” and “What are their comorbidities?” In the elderly population, I often will start with a doublet-based therapy, either lenalidomide and dexamethasone or bortezomib and dexamethasone, and add a third drug.

For instance, I’ll start with Revlimid [lenalidomide] and dexamethasone and add bortezomib, so they would get RVD, a triplet. But I’ll do it in sequential ways, so that I can watch their toxicity very closely. The other thing is that comorbidities play a big role in what we select. With patients who have baseline neuropathy, we try to avoid medications like bortezomib, which may cause further neuropathy.

If the patient has significant renal insufficiency, sometimes we will avoid lenalidomide-based therapy and we’ll use bortezomib as the first regimen. Also, with some people who have diabetes or hypertension, blood pressure that’s out of control, I’ll avoid steroids. I’ll really dose reduce the dexamethasone in those patients. I really believe that, especially in the newly-diagnosed patient, it’s personalized medicine in the way we start medications, the way we continue medicines, and the way we dose adjust regimens as we treat them.

For frontline therapy for the unfit or the frail patients, there are regimens that we can use. There is an RVD-lite regimen where the lenalidomide, the bortezomib, and the dexamethasone are markedly dose reduced. It’s really trying to give the triplet-based therapy, but giving it in a way that the patient, especially this frail patient, is going to be able to tolerate it. There are a lot of dose reductions for many of the medications in the elderly and frail patients. And I would encourage everybody to look for those dose reductions—they’re online—prior to starting any therapy for almost all the myeloma medications.

Transcript Edited for Clarity 
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