Treatment and Management of Multiple Myeloma
The following is a lightly edited transcript of a follow-up teleconference discussion on treating patients with multiple myeloma in the VHA. For more information and the original conversation, visit FedPrac.com/AVAHOupdates.
Use of Bisphosphonates
Dr. Cosgriff. Myeloma metastasizes to bone, and it is one of the common sites of metastatic disease. It poses some interesting complications, whether it is from hypercalcemia due to metastatic sites, or pain syndromes. Bisphosphonates are indicated for myeloma, and they have been for years. Interestingly, unlike some of the other disease, the use of bisphosphonates induces apoptosis in myeloma. So we have seen some disease control with these agents.
The 2 bisphosphonates that are available for use are pamidronate and zoledronic acid. At the VA Portland Health Care System (VAPORHCS), we have been
using pamidronate exclusively for individuals with myeloma. There was a 2003 paper that evaluated the use of bisphosphonates for skeletal-related events in myeloma and in patients with metastatic breast cancer.2 In the subset analysis of myeloma patients with the bisphosphonates, there was no difference between pamidronate and zoledronic acid.
At the time, zoledronic acid was significantly more expensive than pamidronate, and so VAPORHCS opted to use pamidronate as a cost-saving measure. But there are the other reasons for picking pamidronate: Zoledronic acid has some dose recommendations and guidelines for individuals with renal failure, which is often a significant problem in patients with myeloma as well. To get around dose adjustments that need to be made for zoledronic acid, VAPORHCS switched to pamidronate, which is looser with the recommendations on renal failure.
Earlier use criteria, like the National Comprehensive Cancer Network guidelines, stated that if the renal failure was due to the disease itself and not some other outlying factor, a full 90-mg dose of pamidronate could still be used. That comment has since been removed. We still pay attention to it and reduce pamidronate dosing to 60 mg for patients with renal failure.
The prices for zoledronic acid have dropped significantly since it became a generic. The nice thing about zoledronic acid is that it has a short infusion time of 15 minutes. As chair space becomes a problem—VAPHCS has significant issues with that—zoledronic acid looks more and more attractive. The FDA label states that pamidronate should be infused over 4 hours, but VAPHCS typically has been infusing it for 3 hours.
It should be noted that denosumab (XGEVA), a monoclonal antibody that also is targeted for hypercalcemia, has been specifically excluded for myeloma. It
has no FDA indication for myeloma. It does have an indication for hypercalcemia. Whether or not you can state that the patient with myeloma is hypercalcemic, and that’s the reason you want to use it, it starts crossing into some gray area. The drug is still significantly more expensive and it seems to have similar efficacy rates compared with both pamidronate and zoledronic acid, so VAPHCS limits its use to individuals who would otherwise be contraindicated to zoledronic acid or pamidronate due to renal failure.
Dr. Ascensão. How often do you give it, every month, every 3 months?
Dr. Cosgriff. Currently, VAPORHCS is giving bisphosphonates every month whether in the chemotherapy unit or in the short stay unit. We are starting to reevaluate that. I have heard some emerging data that suggest we can use it once a quarter and get the same results. Those data are still emerging. It would be nice to be able to reduce the infusion frequency. But bisphosphonates adhere to bone and get incorporated into the bone matrix and stay there for an extended period of time, upwards of 6 months to a year, as with zoledronic acid.
