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Case Study 2: An Elderly Patient With 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: Monday, Mar 05, 2018



Transcript: 

Thomas G. Martin, MD: In this case, an 81-year-old woman presented with fatigue and was found to have anemia. In fact, she had some pancytopenia. She had low neutrophils, she had low platelets, she had some anemia, and then she was found to have a monoclonal protein. On x-rays, she was found to have bone lesions and advanced bone disease, and she was found to have an elevation in her creatinine with a lower creatinine clearance. Now, it is typical in an older patient who has multiple myeloma that they have comorbidities: pancytopenia and renal insufficiency.

I would have, for this case, done a 24-hour urine test to see if, are they spilling myeloma protein in the urine. Do they have renal insufficiency from myeloma? Or is their creatinine elevated just because of their age? In this patient, it might just be because of their age. We may make some treatment decisions based on that. Now, this patient presented with about 20% of plasma cells in the bone marrow and the most common chromosomal abnormality: translocation (11;14). That happens in about 20% of patients with multiple myeloma and puts her in a standard-risk group of patients.

Now, if we look at risk in assessing the stage of this patient, she has an elevation in her beta-2 microglobulin: 6.2 mcg/mL. By the International Staging System, that would make her stage 3. She did have preserved albumin of 3.8 g/dL, but she’s still international stage 3. There’s now a revised International Staging System that takes into consideration cytogenetics. So, she would be revised international stage 2. Now, if we look at just the regular Durie-Salmon Staging System, which takes into account calcium, hemoglobin, the level of M protein, and the volume of bone disease, because she has advanced bone disease she would have Durie-Salmon stage 3 disease.

Rafael Fonseca, MD: In 2017, as we approach patients who have newly diagnosed myeloma but are of advanced age—that would be someone over the age of 80—we still consider risk status. I think I’ve mentioned in other venues that we don’t want to undertreat patients who could potentially benefit from important drugs, such as a proteasome inhibitor. So, for a patient who is elderly who has a t(4;14), we would probably start on treatment with VRd. There are some patients who have such comorbidities that we may start on a doublet, something like Rd. This case is very interesting, and I will allude to that as we talk about therapy for the relapse.

This patient had t(11;14), which is present in about 15% of myeloma patients, and this has turned out to be more tricky than we thought. Fifteen years ago, t(11;14) was a good prognostic marker, and the reason for that is most patients were being treated with alkylators. As all myelomas have improved over the years, t(4;14) has remained stagnant. Nowadays, you’re better off if you have a t(4;14) than if you have a t(11;14) at the time of diagnosis. We’ll talk about that, about the options for relapse in a patient like this, but I would say if the person is otherwise fit and willing and capable, a triplet would be indicated as first-line therapy for their disease.

One of the things we have learned in myeloma is that chronicity of therapy is important. Maybe we’ll have a future, hopefully, where a patient can be treated for a week, we’ll close the book, and it will all be done because there’s a high cure rate. But nowadays, that’s not the situation. In fact, there are a number of studies, like the MM-015 study or the FIRST study, that have shown chronicity of therapy is important. We have several studies that now show the importance of maintenance post stem cell transplant.

Most recently, a meta-analysis was published in the Journal of Clinical Oncology by Dr. McCarthy. Those same principles have been used for patients who are elderly who received induction therapy. So, if a patient received 8 cycles of VRd, we don’t just stop therapy. For most of those patients, we would actually transition to a maintenance approach, very much like you would do post transplant. There are different opinions for how long you would do that. I say there’s the American way, which is usually indefinite until there is either progression or intolerance, or the European way, which is more time limited to maybe 1 or 2 years. I would say at the bare minimum, I would try to shoot for a year. We understand it’s difficult sometimes, although much easier being the doctor. But if a patient is going great, they’re tolerating their medication, and they’re under control, l would be inclined to continue therapy.

Transcript Edited for Clarity 
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Transcript: 

Thomas G. Martin, MD: In this case, an 81-year-old woman presented with fatigue and was found to have anemia. In fact, she had some pancytopenia. She had low neutrophils, she had low platelets, she had some anemia, and then she was found to have a monoclonal protein. On x-rays, she was found to have bone lesions and advanced bone disease, and she was found to have an elevation in her creatinine with a lower creatinine clearance. Now, it is typical in an older patient who has multiple myeloma that they have comorbidities: pancytopenia and renal insufficiency.

I would have, for this case, done a 24-hour urine test to see if, are they spilling myeloma protein in the urine. Do they have renal insufficiency from myeloma? Or is their creatinine elevated just because of their age? In this patient, it might just be because of their age. We may make some treatment decisions based on that. Now, this patient presented with about 20% of plasma cells in the bone marrow and the most common chromosomal abnormality: translocation (11;14). That happens in about 20% of patients with multiple myeloma and puts her in a standard-risk group of patients.

Now, if we look at risk in assessing the stage of this patient, she has an elevation in her beta-2 microglobulin: 6.2 mcg/mL. By the International Staging System, that would make her stage 3. She did have preserved albumin of 3.8 g/dL, but she’s still international stage 3. There’s now a revised International Staging System that takes into consideration cytogenetics. So, she would be revised international stage 2. Now, if we look at just the regular Durie-Salmon Staging System, which takes into account calcium, hemoglobin, the level of M protein, and the volume of bone disease, because she has advanced bone disease she would have Durie-Salmon stage 3 disease.

Rafael Fonseca, MD: In 2017, as we approach patients who have newly diagnosed myeloma but are of advanced age—that would be someone over the age of 80—we still consider risk status. I think I’ve mentioned in other venues that we don’t want to undertreat patients who could potentially benefit from important drugs, such as a proteasome inhibitor. So, for a patient who is elderly who has a t(4;14), we would probably start on treatment with VRd. There are some patients who have such comorbidities that we may start on a doublet, something like Rd. This case is very interesting, and I will allude to that as we talk about therapy for the relapse.

This patient had t(11;14), which is present in about 15% of myeloma patients, and this has turned out to be more tricky than we thought. Fifteen years ago, t(11;14) was a good prognostic marker, and the reason for that is most patients were being treated with alkylators. As all myelomas have improved over the years, t(4;14) has remained stagnant. Nowadays, you’re better off if you have a t(4;14) than if you have a t(11;14) at the time of diagnosis. We’ll talk about that, about the options for relapse in a patient like this, but I would say if the person is otherwise fit and willing and capable, a triplet would be indicated as first-line therapy for their disease.

One of the things we have learned in myeloma is that chronicity of therapy is important. Maybe we’ll have a future, hopefully, where a patient can be treated for a week, we’ll close the book, and it will all be done because there’s a high cure rate. But nowadays, that’s not the situation. In fact, there are a number of studies, like the MM-015 study or the FIRST study, that have shown chronicity of therapy is important. We have several studies that now show the importance of maintenance post stem cell transplant.

Most recently, a meta-analysis was published in the Journal of Clinical Oncology by Dr. McCarthy. Those same principles have been used for patients who are elderly who received induction therapy. So, if a patient received 8 cycles of VRd, we don’t just stop therapy. For most of those patients, we would actually transition to a maintenance approach, very much like you would do post transplant. There are different opinions for how long you would do that. I say there’s the American way, which is usually indefinite until there is either progression or intolerance, or the European way, which is more time limited to maybe 1 or 2 years. I would say at the bare minimum, I would try to shoot for a year. We understand it’s difficult sometimes, although much easier being the doctor. But if a patient is going great, they’re tolerating their medication, and they’re under control, l would be inclined to continue therapy.

Transcript Edited for Clarity 
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