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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.
