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Multiple Myeloma: Optimizing Approaches to Transplant

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: Monday, Jan 29, 2018



Transcript: 

Rafael Fonseca, MD: When we think about conditioning regimens for a patient who has been newly diagnosed and is moving on to stem-cell transplant, we have recommended, for most patients, a combination of bortezomib, lenalidomide, and dexamethasone. In fact, we present that as part of our consensus recommendations by the Mayo Clinic, the mSMART recommendations, which are available at msmart.org. Now, we did add the variation that for those patients with high-risk disease, one could consider carfilzomib-based induction.

There are a lot of questions. We traditionally do about 4 cycles, but should you keep going if the patient is still responding? How far along do you take that regimen until you decide you should move to transplant? The standard now is about 4 months. Other questions are coming forward, like should we be testing the bone marrow? Should we be testing for MRD before stem-cell transplant? We currently don’t. We do that post–stem-cell transplant, but I think that is part of the process of clinical research that is currently ongoing.

Gareth Morgan, MD, PhD: The question about what the best conditioning regimen is for transplantation is really interesting. It’s a historic fact that 200 mg/m2 of melphalan is the optimum regimen. People introduced total-body radiation to that and it increased toxicity. Our German colleagues increased the dose to 220 mg/m2, and it increased toxicity and early deaths. So we settled almost universally on the use of melphalan. There are other regimens such as BEAM, but there’s much less evidence for BEAM. But sometimes in a patient who has relapsed and has already been exposed to melphalan, it’s possible to consider using BEAM.

There are a number of lines of evidence that tell you when it’s optimum to use a transplant. I believe all the evidence stacks up for using it in newly diagnosed patients, but some believe you should use it at first relapse. That’s based on a study done by a French group led by Jean-Paul Fermand, which seemed to suggest that the survival was the same if you did the transplant up front or at relapse. The problem is that study is now very, very old. The novel agents weren’t available at that time, and even that study supported doing the transplant up front because the first disease-free period was very long, and that’s a time when myeloma patients have their best survival and best quality of life.

Thomas G. Martin, MD: Transplantation occurs in about a quarter of the patients with multiple myeloma, and it’s all autologous transplant at this time. And 75% of patients don’t undergo transplant for a variety of reasons. The majority of them are too old or they have comorbidities, and they’re not a candidate. But for the people with whom we’re going to do transplant—in that 25% of patients—with maybe 30% of those patients who get a transplant, I like to do the transplant right at remission.

Now the actual timing of when to do it—whether it’s after 4 cycles, 6 cycles, or 8 cycles—really depends on how they responded to their initial therapy. I think all of us in the myeloma community would prefer patients to be in what we call a very good partial remission, or a VGPR, to have at least a 90% reduction in their myeloma burden, before they go to transplant. Because then, posttransplant, they’re more likely to get a very deep response.

Transcript Edited for Clarity 
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Transcript: 

Rafael Fonseca, MD: When we think about conditioning regimens for a patient who has been newly diagnosed and is moving on to stem-cell transplant, we have recommended, for most patients, a combination of bortezomib, lenalidomide, and dexamethasone. In fact, we present that as part of our consensus recommendations by the Mayo Clinic, the mSMART recommendations, which are available at msmart.org. Now, we did add the variation that for those patients with high-risk disease, one could consider carfilzomib-based induction.

There are a lot of questions. We traditionally do about 4 cycles, but should you keep going if the patient is still responding? How far along do you take that regimen until you decide you should move to transplant? The standard now is about 4 months. Other questions are coming forward, like should we be testing the bone marrow? Should we be testing for MRD before stem-cell transplant? We currently don’t. We do that post–stem-cell transplant, but I think that is part of the process of clinical research that is currently ongoing.

Gareth Morgan, MD, PhD: The question about what the best conditioning regimen is for transplantation is really interesting. It’s a historic fact that 200 mg/m2 of melphalan is the optimum regimen. People introduced total-body radiation to that and it increased toxicity. Our German colleagues increased the dose to 220 mg/m2, and it increased toxicity and early deaths. So we settled almost universally on the use of melphalan. There are other regimens such as BEAM, but there’s much less evidence for BEAM. But sometimes in a patient who has relapsed and has already been exposed to melphalan, it’s possible to consider using BEAM.

There are a number of lines of evidence that tell you when it’s optimum to use a transplant. I believe all the evidence stacks up for using it in newly diagnosed patients, but some believe you should use it at first relapse. That’s based on a study done by a French group led by Jean-Paul Fermand, which seemed to suggest that the survival was the same if you did the transplant up front or at relapse. The problem is that study is now very, very old. The novel agents weren’t available at that time, and even that study supported doing the transplant up front because the first disease-free period was very long, and that’s a time when myeloma patients have their best survival and best quality of life.

Thomas G. Martin, MD: Transplantation occurs in about a quarter of the patients with multiple myeloma, and it’s all autologous transplant at this time. And 75% of patients don’t undergo transplant for a variety of reasons. The majority of them are too old or they have comorbidities, and they’re not a candidate. But for the people with whom we’re going to do transplant—in that 25% of patients—with maybe 30% of those patients who get a transplant, I like to do the transplant right at remission.

Now the actual timing of when to do it—whether it’s after 4 cycles, 6 cycles, or 8 cycles—really depends on how they responded to their initial therapy. I think all of us in the myeloma community would prefer patients to be in what we call a very good partial remission, or a VGPR, to have at least a 90% reduction in their myeloma burden, before they go to transplant. Because then, posttransplant, they’re more likely to get a very deep response.

Transcript Edited for Clarity 
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