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Case Study 1: Follow-Up Strategies for 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: Tuesday, Feb 20, 2018



Transcript: 

Thomas G. Martin, MD: When a patient like this undergoes transplant, typically at 3 months posttransplant we’ll do a bone marrow biopsy and an assessment of their myeloma burden. That point in time is when we start them on maintenance-based therapy. The standard follow-up for maintenance-based therapy is an every-3-month assessment of myeloma proteins. It’s more commonly monthly, or sometimes every 4 to 6 weeks. We need to assess their CBC; we need to assess their other blood tests to make sure there is no organ toxicity. But in fact, the assessment of myeloma is really every 3 months with laboratory testing.

Now, some of these patients can relapse outside of the bone marrow, and I routinely will get a PET scan yearly for these patients posttransplant. At about 12 months posttransplant, they’ll get a PET-CT scan, and typically we’ll do it yearly. If it’s somebody who has had extramedullary disease and has mostly relapsed with extramedullary disease, then I follow the PET-CTs more frequently, sometimes every 4 to 6 months.

In the posttransplant setting, we’ve now been assessing patients at their bone marrow biopsy at 3 months posttransplant, and potentially a year posttransplant, with minimal residual disease or MRD testing. The benefit of MRD testing at the current time is it just tells us the prognosis. It doesn’t help us select therapy; it doesn’t help us change therapy at the current time. It is merely a measure of prognosis. Those patients who are MRD-negative do better than patients who are MRD-positive. In fact, patients who are in complete remission and are MRD-positive really do as well or the same as patients who have just achieved a partial remission. So, having a CR is only good, according to a small amount of data that we have right now, if you’ve achieved MRD negativity.

It’s not quite ready for prime time, and that’s a problem. I think it will be several years before it’s going to be ready for prime time, for 2 reasons. One is that the mechanism we use to assess MRD is not available to all places and all practices in the United States. There are 2 ways to do it. One is a Uroflow test that looks at a 12-color flow cytometry test to really try to pick out 1 in a million or 1 in 105 cells. That Uroflow test is only available at a few centers across the country at the current time. Over the next 2 years, they will be available more commonly at a lot of the transplant centers across the United States and doctors will be able to send samples from their patients.

The other way to do it is by next-generation sequencing or PCR testing. There’s a company, Adaptive Biotechnologies, that’s offering this test to patients with myeloma, and it requires having a baseline sample. We don’t have a baseline sample from the original bone marrow biopsy in everyone. In fact, we probably lose 20% to 30% of patients regarding our ability to look at MRD through PCR testing because we don’t have that initial PCR. Maybe in 2 or 3 years from now, it’ll be routine that when somebody is newly diagnosed with myeloma and gets a bone marrow biopsy, they’ll have DNA sent for their DNA fingerprint of myeloma, which looks at the immunoglobulin and heavy-chain and light-chain rearrangements.

Transcript Edited for Clarity 
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Transcript: 

Thomas G. Martin, MD: When a patient like this undergoes transplant, typically at 3 months posttransplant we’ll do a bone marrow biopsy and an assessment of their myeloma burden. That point in time is when we start them on maintenance-based therapy. The standard follow-up for maintenance-based therapy is an every-3-month assessment of myeloma proteins. It’s more commonly monthly, or sometimes every 4 to 6 weeks. We need to assess their CBC; we need to assess their other blood tests to make sure there is no organ toxicity. But in fact, the assessment of myeloma is really every 3 months with laboratory testing.

Now, some of these patients can relapse outside of the bone marrow, and I routinely will get a PET scan yearly for these patients posttransplant. At about 12 months posttransplant, they’ll get a PET-CT scan, and typically we’ll do it yearly. If it’s somebody who has had extramedullary disease and has mostly relapsed with extramedullary disease, then I follow the PET-CTs more frequently, sometimes every 4 to 6 months.

In the posttransplant setting, we’ve now been assessing patients at their bone marrow biopsy at 3 months posttransplant, and potentially a year posttransplant, with minimal residual disease or MRD testing. The benefit of MRD testing at the current time is it just tells us the prognosis. It doesn’t help us select therapy; it doesn’t help us change therapy at the current time. It is merely a measure of prognosis. Those patients who are MRD-negative do better than patients who are MRD-positive. In fact, patients who are in complete remission and are MRD-positive really do as well or the same as patients who have just achieved a partial remission. So, having a CR is only good, according to a small amount of data that we have right now, if you’ve achieved MRD negativity.

It’s not quite ready for prime time, and that’s a problem. I think it will be several years before it’s going to be ready for prime time, for 2 reasons. One is that the mechanism we use to assess MRD is not available to all places and all practices in the United States. There are 2 ways to do it. One is a Uroflow test that looks at a 12-color flow cytometry test to really try to pick out 1 in a million or 1 in 105 cells. That Uroflow test is only available at a few centers across the country at the current time. Over the next 2 years, they will be available more commonly at a lot of the transplant centers across the United States and doctors will be able to send samples from their patients.

The other way to do it is by next-generation sequencing or PCR testing. There’s a company, Adaptive Biotechnologies, that’s offering this test to patients with myeloma, and it requires having a baseline sample. We don’t have a baseline sample from the original bone marrow biopsy in everyone. In fact, we probably lose 20% to 30% of patients regarding our ability to look at MRD through PCR testing because we don’t have that initial PCR. Maybe in 2 or 3 years from now, it’ll be routine that when somebody is newly diagnosed with myeloma and gets a bone marrow biopsy, they’ll have DNA sent for their DNA fingerprint of myeloma, which looks at the immunoglobulin and heavy-chain and light-chain rearrangements.

Transcript Edited for Clarity 
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