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Discussants: Matt Kalaycio, MD1; Sagar Lonial, MD2
From Cleveland Clinic, Cleveland, OH1; Emory University, Atlanta, GA2
Address for correspondence: Matt Kalaycio, MD, Cleveland Clinic Main Campus, Mail Code R32, 9500 Euclid Avenue, Cleveland, OH 44195
E-mail: [email protected]
Biographical sketch:
Dr. Kalaycio has been published in numerous scientific publications including Bone Marrow Transplantation, Journal of Clinical Oncology, and Leukemia. He also is the editor of a book on leukemia and co-editor of a book on clinical malignant hematology. His research interests focus on testing new treatments for leukemia.
Dr. Kalaycio received his degree from West Virginia University School of Medicine in Morgantown. He completed his residency in internal medicine at Mercy Hospital of Pittsburgh and fellowships in hematology and medical oncology and bone marrow transplantation at Cleveland Clinic.
Dr. Lonial is involved in numerous professional organizations including the American Society of Clinical Oncology, American Society of Hematology, and the American Society for Blood and Marrow Transplantation. He serves as Vice Chair of the Myeloma Committee in the Eastern Cooperative Oncology Group and as Chair of the Steering Committee for the Multiple Myeloma Research Consortium. Additionally, he is on the board of directors for the International Myeloma Society, and on the scientific Advisory Board for the International Myeloma Foundation.
Practice Guidelines
Dr. Kalaycio: I'm trying to avoid some of the controversy surrounding what treatment we should start with, or continue with. I think that literature is difficult to digest in a small soundbite. I’m more interested for this particular conversation in discussing some of the practicalities of managing patients with a newly diagnosed myeloma—regarding some of the things that a large center might take for granted, whereas a clinician in a smaller practice might not have as much experience, and might not know exactly how to handle. I think that literature is difficult to digest in a small soundbite. I’m more interested for this particular conversation in discussing some of the practicalities of managing patients with a newly diagnosed myeloma—regarding some of the things that a large center might take for granted, whereas a clinician in a smaller practice might not have as much experience, and might not know exactly how to handle. For example, current recommendations for bisphosphonates can be confusing. Although we use them, it's often an interesting discussion about which one we should use. Do you have a preference in your practice, and do you use criteria one way or another to pick one over the other?
Dr. Lonial: Yes, I think you're absolutely correct that the guidelines are a little confusing on how to do this. I'll tell you just from a convenience perspective for patients, we tend to use zoledronic acid as our go-to bisphosphonate, predominately because it's a shorter duration. We usually give it over 30 minutes. Patients prefer that sort of shorter infusion time. For patients that have any level of renal dysfunction—what I'm usually thinking about is creatinine levels over 2 mg/dL—we may use pamidronate as our preferential bisphosphonate. We'll even dose bisphosphonates. One of the things I think often gets lost in the bisphosphonate literature is that pharmacies will not release the drug because the patient's creatinine is 2.5 mg/dL or 3 mg/dL. What they don't realize is that no one gets renal failure from a single dose of bisphosphonate—it's really a cumulative effect over a long period of time.
For patients who have bone disease, I think the use of bisphosphonates is really important in terms of reducing the risk of skeletal events and fractures, which we see much less frequently now. Figuring out how to optimally do that—even in patients with renal dysfunction, I think—is really important. We disagree with the American Society of Clinical Oncology (ASCO) guidelines, in terms of how to approach giving bisphosphonates. Our approach is that any patient with myeloma (if you look hard enough) has some level of bone disease.
We treat all patients with symptomatic myeloma with bisphosphonates. I think the ASCO guidelines discriminate—only those who have skeletal survey positive should be treated with bisphosphonate. If you look at the Medical Research Council Myeloma IX (MRC IX) trial that treated everybody with bisphosphonates, there was a survival benefit across the board for patients.1
All patients seemed to benefit from the use of bisphosphonates, whether or not they had skeletal survey identified bone disease. In fact, we know that in order for a skeletal survey to be abnormal, 70% of the cortex has to be gone, or eroded, by the disease already. Whereas computed tomographic scans and magnetic resonance imaging will pick it up at much lower levels. I think it's a pretty crude test, and there's a big move in the Myeloma Working Group now to replace skeletal surveys with low-dose whole-body computed tomographic scans, because they're much more accurate, and more predictive.
Dr. Kalaycio: Yes, we're heading in the same direction only with magnetic resonance imaging. Our practice is also informed by that MRC IX trial, and we give bisphosphonates to everybody. In contrast to your practice though, our fallback is pamidronate, and that's because we lost the argument to our pharmacy as to the role of bisphosphonates in contributing to potential renal dysfunction with multiple doses. Our fallback is pamidronate, but certainly from a convenience factor there's a lot to be said for zoledronic acid.
Dr. Lonial: Right.
Dr. Kalaycio: With the application of bisphosphonates, there's also inconsistent application of prophylactic antibiotics for these patients who get plenty of corticosteroids, and immunosuppressives. We typically would treat everyone with vaccines, but we don't routinely use sulfamethoxazole-trimethoprim. I've seen sulfamethoxazole-trimethoprim used off and on depending on where the patient is coming from, and their referral to us. Do you routinely employ prophylactic antibiotics in your practice?
Dr. Lonial: We use sulfamethoxazole-trimethoprim for patients who are getting dexamethasone. We usually start that in cycle 2, because with a lot of our patients, you don't know whether the rash is from sulfamethoxazole-trimethoprim or whether it's from an IMiD. So we'll start an IMiD/PI combination up front, and then after cycle 1 add in the sulfamethoxazole-trimethoprim three times a week as prophylaxis—just as we do in many patients who are getting high-dose dexamethasone as well.
We usually continue the sulfamethoxazole-trimethoprim until they've been off high-dose dexamethasone for a month or two. I think the other piece to add is the antiviral prophylaxis. We have all of our patients across the board on lifelong acyclovir prophylaxis, to reduce the risk of varicella zoster virus (VZV). If you look across the board, a significant fraction of myeloma patients will present with VZV in the last 12 months. I think having a plasma cell disorder certainly puts you at risk for developing VZV reactivation.
We don't routinely recommend the Zostavax vaccine for these patients, because it's a live vaccine. I think the third area building on the prophylaxis concept is the use of a deep vein thrombosis prophylaxis for patients that are receiving IMiDs. One of the areas—I think almost everybody realizes that you need to use it—where we find issues is that physicians or their interventional radiologists will tell the patient to stop aspirin, because they're going to put in a line or they're going to do something else.
What I think people don't realize is that if you stop an aspirin in a patient who's been on an IMiD within 30 days, you're now hypercoagulable. You're actually at a much higher risk of clotting than if you just continued the aspirin or prophylaxis. What I think people don't realize is that if you stop an aspirin in a patient who's been on an IMiD within 30 days, you're now hypercoagulable. You're actually at a much higher risk of clotting than if you just continued the aspirin or prophylaxis. When procedures have to be done in patients who are on an IMiD, even if you stop the IMiD for a week, the risk of thrombosis is there for another three to four weeks. If you're going to stop the aspirin prophylaxis, you have to bridge them, just like you would somebody who's on full-dose anticoagulation for an active clot. We find lots of patients get clots when interventional radiology tells them stop the aspirin. They get a line put in, and they get a clot. That, to me, is an area where clinical practice needs to be informed by the oncologist, because everybody else doesn't understand the risks in the situation.
Dr. Kalaycio: That's an interesting observation that we've not made, with regard to the placement of lines. We've certainly seen clots when aspirin is interrupted whether for surgery, or because someone is stopping it for another reason.
We also use acyclovir prophylactically forever. We do not routinely replace gamma globulin for hypogammaglobulinemia. We would if there were recurrent and relatively severe infections. We don’t typically do it routinely just for low gamma globulin levels. Where do you stand on that?
Dr. Lonial: I completely agree with you. If they've had two or three recurrent infections in one season, then we'll give them intravenous immunoglobulin maybe every month, or every other month, for a couple of doses. We don't just replace the number.
Dr. Kalaycio: Right. For the young patient—under the age of 50 even—with multiple myeloma, whether high risk or low, current guidelines do not suggest the routine use of allogeneic transplant (ALLO) outside of the context of the clinical trial.2 We have conformed to that recommendation here, and I'm curious if you feel the same way at Emory.
Dr. Lonial: Yes, I do. I think in the context of a well-designed trial, it is perfectly appropriate. To me it's all about risk/benefit. I was trained as an ALLO transplanter, so I know the argument. We'll say this is your only chance at long-term cure.
That is true, if you're willing to accept a 10% long-term chance of cure. What is often underplayed is the risk of graft-versus-host disease, and the ongoing risk of relapse that continues to occur, not just one year, but two, three, four, even five years out from the ALLO transplant. I think if it's a risk that a patient is willing to take, and they're making an informed decision, I have no issues with that at all—especially if done in the context of a clinical trial. Outside of that, I think it's a pretty risky proposition.
Dr. Kalaycio: I agree.
1. Morgan GJ, Child JA, Gregory WM, et al. for the National Cancer Research Institute Haematological Oncology Clinical Studies Group. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomized controlled trial. Lancet Oncol. 2011;12(8):743–752.
2. Nooka AK, Kastritis E, Dimopoulos MA, Lonial S. Treatment options for relapsed and refractory multiple myeloma. Blood. 2015;125(20):3085-3099.
Discussants: Matt Kalaycio, MD1; Sagar Lonial, MD2
From Cleveland Clinic, Cleveland, OH1; Emory University, Atlanta, GA2
Address for correspondence: Matt Kalaycio, MD, Cleveland Clinic Main Campus, Mail Code R32, 9500 Euclid Avenue, Cleveland, OH 44195
E-mail: [email protected]
Biographical sketch:
Dr. Kalaycio has been published in numerous scientific publications including Bone Marrow Transplantation, Journal of Clinical Oncology, and Leukemia. He also is the editor of a book on leukemia and co-editor of a book on clinical malignant hematology. His research interests focus on testing new treatments for leukemia.
Dr. Kalaycio received his degree from West Virginia University School of Medicine in Morgantown. He completed his residency in internal medicine at Mercy Hospital of Pittsburgh and fellowships in hematology and medical oncology and bone marrow transplantation at Cleveland Clinic.
Dr. Lonial is involved in numerous professional organizations including the American Society of Clinical Oncology, American Society of Hematology, and the American Society for Blood and Marrow Transplantation. He serves as Vice Chair of the Myeloma Committee in the Eastern Cooperative Oncology Group and as Chair of the Steering Committee for the Multiple Myeloma Research Consortium. Additionally, he is on the board of directors for the International Myeloma Society, and on the scientific Advisory Board for the International Myeloma Foundation.
Practice Guidelines
Dr. Kalaycio: I'm trying to avoid some of the controversy surrounding what treatment we should start with, or continue with. I think that literature is difficult to digest in a small soundbite. I’m more interested for this particular conversation in discussing some of the practicalities of managing patients with a newly diagnosed myeloma—regarding some of the things that a large center might take for granted, whereas a clinician in a smaller practice might not have as much experience, and might not know exactly how to handle. I think that literature is difficult to digest in a small soundbite. I’m more interested for this particular conversation in discussing some of the practicalities of managing patients with a newly diagnosed myeloma—regarding some of the things that a large center might take for granted, whereas a clinician in a smaller practice might not have as much experience, and might not know exactly how to handle. For example, current recommendations for bisphosphonates can be confusing. Although we use them, it's often an interesting discussion about which one we should use. Do you have a preference in your practice, and do you use criteria one way or another to pick one over the other?
Dr. Lonial: Yes, I think you're absolutely correct that the guidelines are a little confusing on how to do this. I'll tell you just from a convenience perspective for patients, we tend to use zoledronic acid as our go-to bisphosphonate, predominately because it's a shorter duration. We usually give it over 30 minutes. Patients prefer that sort of shorter infusion time. For patients that have any level of renal dysfunction—what I'm usually thinking about is creatinine levels over 2 mg/dL—we may use pamidronate as our preferential bisphosphonate. We'll even dose bisphosphonates. One of the things I think often gets lost in the bisphosphonate literature is that pharmacies will not release the drug because the patient's creatinine is 2.5 mg/dL or 3 mg/dL. What they don't realize is that no one gets renal failure from a single dose of bisphosphonate—it's really a cumulative effect over a long period of time.
For patients who have bone disease, I think the use of bisphosphonates is really important in terms of reducing the risk of skeletal events and fractures, which we see much less frequently now. Figuring out how to optimally do that—even in patients with renal dysfunction, I think—is really important. We disagree with the American Society of Clinical Oncology (ASCO) guidelines, in terms of how to approach giving bisphosphonates. Our approach is that any patient with myeloma (if you look hard enough) has some level of bone disease.
We treat all patients with symptomatic myeloma with bisphosphonates. I think the ASCO guidelines discriminate—only those who have skeletal survey positive should be treated with bisphosphonate. If you look at the Medical Research Council Myeloma IX (MRC IX) trial that treated everybody with bisphosphonates, there was a survival benefit across the board for patients.1
All patients seemed to benefit from the use of bisphosphonates, whether or not they had skeletal survey identified bone disease. In fact, we know that in order for a skeletal survey to be abnormal, 70% of the cortex has to be gone, or eroded, by the disease already. Whereas computed tomographic scans and magnetic resonance imaging will pick it up at much lower levels. I think it's a pretty crude test, and there's a big move in the Myeloma Working Group now to replace skeletal surveys with low-dose whole-body computed tomographic scans, because they're much more accurate, and more predictive.
Dr. Kalaycio: Yes, we're heading in the same direction only with magnetic resonance imaging. Our practice is also informed by that MRC IX trial, and we give bisphosphonates to everybody. In contrast to your practice though, our fallback is pamidronate, and that's because we lost the argument to our pharmacy as to the role of bisphosphonates in contributing to potential renal dysfunction with multiple doses. Our fallback is pamidronate, but certainly from a convenience factor there's a lot to be said for zoledronic acid.
Dr. Lonial: Right.
Dr. Kalaycio: With the application of bisphosphonates, there's also inconsistent application of prophylactic antibiotics for these patients who get plenty of corticosteroids, and immunosuppressives. We typically would treat everyone with vaccines, but we don't routinely use sulfamethoxazole-trimethoprim. I've seen sulfamethoxazole-trimethoprim used off and on depending on where the patient is coming from, and their referral to us. Do you routinely employ prophylactic antibiotics in your practice?
Dr. Lonial: We use sulfamethoxazole-trimethoprim for patients who are getting dexamethasone. We usually start that in cycle 2, because with a lot of our patients, you don't know whether the rash is from sulfamethoxazole-trimethoprim or whether it's from an IMiD. So we'll start an IMiD/PI combination up front, and then after cycle 1 add in the sulfamethoxazole-trimethoprim three times a week as prophylaxis—just as we do in many patients who are getting high-dose dexamethasone as well.
We usually continue the sulfamethoxazole-trimethoprim until they've been off high-dose dexamethasone for a month or two. I think the other piece to add is the antiviral prophylaxis. We have all of our patients across the board on lifelong acyclovir prophylaxis, to reduce the risk of varicella zoster virus (VZV). If you look across the board, a significant fraction of myeloma patients will present with VZV in the last 12 months. I think having a plasma cell disorder certainly puts you at risk for developing VZV reactivation.
We don't routinely recommend the Zostavax vaccine for these patients, because it's a live vaccine. I think the third area building on the prophylaxis concept is the use of a deep vein thrombosis prophylaxis for patients that are receiving IMiDs. One of the areas—I think almost everybody realizes that you need to use it—where we find issues is that physicians or their interventional radiologists will tell the patient to stop aspirin, because they're going to put in a line or they're going to do something else.
What I think people don't realize is that if you stop an aspirin in a patient who's been on an IMiD within 30 days, you're now hypercoagulable. You're actually at a much higher risk of clotting than if you just continued the aspirin or prophylaxis. What I think people don't realize is that if you stop an aspirin in a patient who's been on an IMiD within 30 days, you're now hypercoagulable. You're actually at a much higher risk of clotting than if you just continued the aspirin or prophylaxis. When procedures have to be done in patients who are on an IMiD, even if you stop the IMiD for a week, the risk of thrombosis is there for another three to four weeks. If you're going to stop the aspirin prophylaxis, you have to bridge them, just like you would somebody who's on full-dose anticoagulation for an active clot. We find lots of patients get clots when interventional radiology tells them stop the aspirin. They get a line put in, and they get a clot. That, to me, is an area where clinical practice needs to be informed by the oncologist, because everybody else doesn't understand the risks in the situation.
Dr. Kalaycio: That's an interesting observation that we've not made, with regard to the placement of lines. We've certainly seen clots when aspirin is interrupted whether for surgery, or because someone is stopping it for another reason.
We also use acyclovir prophylactically forever. We do not routinely replace gamma globulin for hypogammaglobulinemia. We would if there were recurrent and relatively severe infections. We don’t typically do it routinely just for low gamma globulin levels. Where do you stand on that?
Dr. Lonial: I completely agree with you. If they've had two or three recurrent infections in one season, then we'll give them intravenous immunoglobulin maybe every month, or every other month, for a couple of doses. We don't just replace the number.
Dr. Kalaycio: Right. For the young patient—under the age of 50 even—with multiple myeloma, whether high risk or low, current guidelines do not suggest the routine use of allogeneic transplant (ALLO) outside of the context of the clinical trial.2 We have conformed to that recommendation here, and I'm curious if you feel the same way at Emory.
Dr. Lonial: Yes, I do. I think in the context of a well-designed trial, it is perfectly appropriate. To me it's all about risk/benefit. I was trained as an ALLO transplanter, so I know the argument. We'll say this is your only chance at long-term cure.
That is true, if you're willing to accept a 10% long-term chance of cure. What is often underplayed is the risk of graft-versus-host disease, and the ongoing risk of relapse that continues to occur, not just one year, but two, three, four, even five years out from the ALLO transplant. I think if it's a risk that a patient is willing to take, and they're making an informed decision, I have no issues with that at all—especially if done in the context of a clinical trial. Outside of that, I think it's a pretty risky proposition.
Dr. Kalaycio: I agree.
Discussants: Matt Kalaycio, MD1; Sagar Lonial, MD2
From Cleveland Clinic, Cleveland, OH1; Emory University, Atlanta, GA2
Address for correspondence: Matt Kalaycio, MD, Cleveland Clinic Main Campus, Mail Code R32, 9500 Euclid Avenue, Cleveland, OH 44195
E-mail: [email protected]
Biographical sketch:
Dr. Kalaycio has been published in numerous scientific publications including Bone Marrow Transplantation, Journal of Clinical Oncology, and Leukemia. He also is the editor of a book on leukemia and co-editor of a book on clinical malignant hematology. His research interests focus on testing new treatments for leukemia.
Dr. Kalaycio received his degree from West Virginia University School of Medicine in Morgantown. He completed his residency in internal medicine at Mercy Hospital of Pittsburgh and fellowships in hematology and medical oncology and bone marrow transplantation at Cleveland Clinic.
Dr. Lonial is involved in numerous professional organizations including the American Society of Clinical Oncology, American Society of Hematology, and the American Society for Blood and Marrow Transplantation. He serves as Vice Chair of the Myeloma Committee in the Eastern Cooperative Oncology Group and as Chair of the Steering Committee for the Multiple Myeloma Research Consortium. Additionally, he is on the board of directors for the International Myeloma Society, and on the scientific Advisory Board for the International Myeloma Foundation.
Practice Guidelines
Dr. Kalaycio: I'm trying to avoid some of the controversy surrounding what treatment we should start with, or continue with. I think that literature is difficult to digest in a small soundbite. I’m more interested for this particular conversation in discussing some of the practicalities of managing patients with a newly diagnosed myeloma—regarding some of the things that a large center might take for granted, whereas a clinician in a smaller practice might not have as much experience, and might not know exactly how to handle. I think that literature is difficult to digest in a small soundbite. I’m more interested for this particular conversation in discussing some of the practicalities of managing patients with a newly diagnosed myeloma—regarding some of the things that a large center might take for granted, whereas a clinician in a smaller practice might not have as much experience, and might not know exactly how to handle. For example, current recommendations for bisphosphonates can be confusing. Although we use them, it's often an interesting discussion about which one we should use. Do you have a preference in your practice, and do you use criteria one way or another to pick one over the other?
Dr. Lonial: Yes, I think you're absolutely correct that the guidelines are a little confusing on how to do this. I'll tell you just from a convenience perspective for patients, we tend to use zoledronic acid as our go-to bisphosphonate, predominately because it's a shorter duration. We usually give it over 30 minutes. Patients prefer that sort of shorter infusion time. For patients that have any level of renal dysfunction—what I'm usually thinking about is creatinine levels over 2 mg/dL—we may use pamidronate as our preferential bisphosphonate. We'll even dose bisphosphonates. One of the things I think often gets lost in the bisphosphonate literature is that pharmacies will not release the drug because the patient's creatinine is 2.5 mg/dL or 3 mg/dL. What they don't realize is that no one gets renal failure from a single dose of bisphosphonate—it's really a cumulative effect over a long period of time.
For patients who have bone disease, I think the use of bisphosphonates is really important in terms of reducing the risk of skeletal events and fractures, which we see much less frequently now. Figuring out how to optimally do that—even in patients with renal dysfunction, I think—is really important. We disagree with the American Society of Clinical Oncology (ASCO) guidelines, in terms of how to approach giving bisphosphonates. Our approach is that any patient with myeloma (if you look hard enough) has some level of bone disease.
We treat all patients with symptomatic myeloma with bisphosphonates. I think the ASCO guidelines discriminate—only those who have skeletal survey positive should be treated with bisphosphonate. If you look at the Medical Research Council Myeloma IX (MRC IX) trial that treated everybody with bisphosphonates, there was a survival benefit across the board for patients.1
All patients seemed to benefit from the use of bisphosphonates, whether or not they had skeletal survey identified bone disease. In fact, we know that in order for a skeletal survey to be abnormal, 70% of the cortex has to be gone, or eroded, by the disease already. Whereas computed tomographic scans and magnetic resonance imaging will pick it up at much lower levels. I think it's a pretty crude test, and there's a big move in the Myeloma Working Group now to replace skeletal surveys with low-dose whole-body computed tomographic scans, because they're much more accurate, and more predictive.
Dr. Kalaycio: Yes, we're heading in the same direction only with magnetic resonance imaging. Our practice is also informed by that MRC IX trial, and we give bisphosphonates to everybody. In contrast to your practice though, our fallback is pamidronate, and that's because we lost the argument to our pharmacy as to the role of bisphosphonates in contributing to potential renal dysfunction with multiple doses. Our fallback is pamidronate, but certainly from a convenience factor there's a lot to be said for zoledronic acid.
Dr. Lonial: Right.
Dr. Kalaycio: With the application of bisphosphonates, there's also inconsistent application of prophylactic antibiotics for these patients who get plenty of corticosteroids, and immunosuppressives. We typically would treat everyone with vaccines, but we don't routinely use sulfamethoxazole-trimethoprim. I've seen sulfamethoxazole-trimethoprim used off and on depending on where the patient is coming from, and their referral to us. Do you routinely employ prophylactic antibiotics in your practice?
Dr. Lonial: We use sulfamethoxazole-trimethoprim for patients who are getting dexamethasone. We usually start that in cycle 2, because with a lot of our patients, you don't know whether the rash is from sulfamethoxazole-trimethoprim or whether it's from an IMiD. So we'll start an IMiD/PI combination up front, and then after cycle 1 add in the sulfamethoxazole-trimethoprim three times a week as prophylaxis—just as we do in many patients who are getting high-dose dexamethasone as well.
We usually continue the sulfamethoxazole-trimethoprim until they've been off high-dose dexamethasone for a month or two. I think the other piece to add is the antiviral prophylaxis. We have all of our patients across the board on lifelong acyclovir prophylaxis, to reduce the risk of varicella zoster virus (VZV). If you look across the board, a significant fraction of myeloma patients will present with VZV in the last 12 months. I think having a plasma cell disorder certainly puts you at risk for developing VZV reactivation.
We don't routinely recommend the Zostavax vaccine for these patients, because it's a live vaccine. I think the third area building on the prophylaxis concept is the use of a deep vein thrombosis prophylaxis for patients that are receiving IMiDs. One of the areas—I think almost everybody realizes that you need to use it—where we find issues is that physicians or their interventional radiologists will tell the patient to stop aspirin, because they're going to put in a line or they're going to do something else.
What I think people don't realize is that if you stop an aspirin in a patient who's been on an IMiD within 30 days, you're now hypercoagulable. You're actually at a much higher risk of clotting than if you just continued the aspirin or prophylaxis. What I think people don't realize is that if you stop an aspirin in a patient who's been on an IMiD within 30 days, you're now hypercoagulable. You're actually at a much higher risk of clotting than if you just continued the aspirin or prophylaxis. When procedures have to be done in patients who are on an IMiD, even if you stop the IMiD for a week, the risk of thrombosis is there for another three to four weeks. If you're going to stop the aspirin prophylaxis, you have to bridge them, just like you would somebody who's on full-dose anticoagulation for an active clot. We find lots of patients get clots when interventional radiology tells them stop the aspirin. They get a line put in, and they get a clot. That, to me, is an area where clinical practice needs to be informed by the oncologist, because everybody else doesn't understand the risks in the situation.
Dr. Kalaycio: That's an interesting observation that we've not made, with regard to the placement of lines. We've certainly seen clots when aspirin is interrupted whether for surgery, or because someone is stopping it for another reason.
We also use acyclovir prophylactically forever. We do not routinely replace gamma globulin for hypogammaglobulinemia. We would if there were recurrent and relatively severe infections. We don’t typically do it routinely just for low gamma globulin levels. Where do you stand on that?
Dr. Lonial: I completely agree with you. If they've had two or three recurrent infections in one season, then we'll give them intravenous immunoglobulin maybe every month, or every other month, for a couple of doses. We don't just replace the number.
Dr. Kalaycio: Right. For the young patient—under the age of 50 even—with multiple myeloma, whether high risk or low, current guidelines do not suggest the routine use of allogeneic transplant (ALLO) outside of the context of the clinical trial.2 We have conformed to that recommendation here, and I'm curious if you feel the same way at Emory.
Dr. Lonial: Yes, I do. I think in the context of a well-designed trial, it is perfectly appropriate. To me it's all about risk/benefit. I was trained as an ALLO transplanter, so I know the argument. We'll say this is your only chance at long-term cure.
That is true, if you're willing to accept a 10% long-term chance of cure. What is often underplayed is the risk of graft-versus-host disease, and the ongoing risk of relapse that continues to occur, not just one year, but two, three, four, even five years out from the ALLO transplant. I think if it's a risk that a patient is willing to take, and they're making an informed decision, I have no issues with that at all—especially if done in the context of a clinical trial. Outside of that, I think it's a pretty risky proposition.
Dr. Kalaycio: I agree.
1. Morgan GJ, Child JA, Gregory WM, et al. for the National Cancer Research Institute Haematological Oncology Clinical Studies Group. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomized controlled trial. Lancet Oncol. 2011;12(8):743–752.
2. Nooka AK, Kastritis E, Dimopoulos MA, Lonial S. Treatment options for relapsed and refractory multiple myeloma. Blood. 2015;125(20):3085-3099.
1. Morgan GJ, Child JA, Gregory WM, et al. for the National Cancer Research Institute Haematological Oncology Clinical Studies Group. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomized controlled trial. Lancet Oncol. 2011;12(8):743–752.
2. Nooka AK, Kastritis E, Dimopoulos MA, Lonial S. Treatment options for relapsed and refractory multiple myeloma. Blood. 2015;125(20):3085-3099.
