I field a lot of questions about bisphosphonates. The two most commonly used for myeloma patients: Aredia and Zometa.
I’m not going to write a sited research paper on the topic. But this post should answer some of the most common patient questions.
Use of bishphosphonates is not without controversy. I remember Mayo Clinic-Rochester administered Aredia instead of the newer Zometa for a number of years. Aredia is infused more slowly; over a two to three hour period. Zometa can be administered (both via IV drip) in as little as 15 minutes, although I’ve always insisted on at least a half hour.
Apparently Mayo Clinic specialists felt there was less risk of developing the most feared bisphosphonate side effect: osteonecrosis of the jaw (ONJ). In 2015, Zometa (manufactured by Novartis) is the overwhelming bisphosphonate choice of myeloma specialists.
I’ve noticed one of the first thing a medical oncologist or myeloma specialist does is get a patient started on Zometa. Compared to other drugs used to treat multiple myeloma, bisphosphonates are relatively safe and innocuous, at least at first. Novartis worked hard earlier this decade proving Zometa has anti-myeloma properties. It is said to help prevent new bone lesions from forming, in addition to helping damaged bones heal and strengthening bones.
Less experienced myeloma patients often think of Zometa as chemotherapy. When I ask someone what myeloma therapy they’re on at a support group or online, they often include Zometa on the list. I think that’s because the drug is administered IV; if it were a pill, I’m guessing it wouldn’t even be mentioned.
Most patients take Zometa without side effects. A few experience flu-like symptoms for an hour or two after an infusion. Others a bit of bone pain. But Zometa is a powerful drug. I know people that have developed ONJ and it isn’t any fun. Osteonecrosis refers to reduced blood flow to a bone or bones. I’m not sure why our jaws seem to be at risk, but once damage starts there’s no way to reverse it. Stopping Zometa at that point is a must; in most cases further damage stops then, too.
What percentage of patients develop ONJ? Only two or three out of every hundred. The odds are even lower if a patient, doctor and dentist work together, making sure there isn’t any major dental work (or injury) at the time of infusion.
Those of you familiar with my writing style may detect a bit of detachment in this post. I have mixed feelings about bisphosphonates. How effective are they?
Myeloma experts overwhelmingly agree that the risk of developing ONJ is not reason enough not to use Zometa. The drug is relatively inexpensive and statistics show it can help, especially at first. Here are excerpts from a Myeloma Beacon article, by Michelle Spector, about Zometa way back in 2010. You may recognize the lead doctor in the article: Dr. Gareth Morgan, now head of the myeloma program at UAMS in Little Rock, Arkansas:
Zometa and Bonefos are both bisphosphonates, which reduce bone loss and fractures by helping to rebuild bone. Zometa is approved for use in the United States; however, Bonefos is not.
Previous pre-clinical and clinical trials have suggested that in addition to preventing bone loss and related complications, Zometa may also have anti-cancer effects. However, no clinical trials have shown that Zometa has anti-myeloma effects. Dr. Morgan suggested during his presentation that Zometa may reduce tumor growth, cause death of myeloma cells, and stimulate the immune system.
Given the results of these past trials, Dr. Morgan and his colleagues evaluated Zometa as an anti-myeloma agent in comparison to Bonefos by comparing the effect the two drugs have on overall survival and progression-free survival in myeloma patients. They also evaluated the drugs’ effects on bone-related complications.
Almost 2,000 newly diagnosed multiple myeloma patients, 70 percent of whom had bone disease, participated in the study. Each participant received either Zometa or Bonefos, in addition to the myeloma therapies they were receiving. At the time of the ASCO presentation, 75 percent of participants had stayed on their bisphosphonate until disease progression, while 25 percent discontinued their bone treatment once their myeloma was stable or in remission.
“Zometa is superior to Bonefos in the prevention of skeletal-related events in patients with newly diagnosed myeloma,” said Dr. Morgan. Twenty-seven percent of the patients receiving Zometa experienced skeletal-related complications, compared to 35 percent of the Bonefos group.
Survival rates were also higher among patients receiving Zometa. Overall survival was 50 months for the Zometa group and 44.5 months for the Bonefos group. Progression-free survival was 19.5 months for the Zometa group and 17.5 months for the Bonefos group. According to Dr. Morgan, a survival advantage of 5.5 months is “clinically significant.”
Side effects were minimal for both treatments, and there was no difference in kidney function deterioration among the Bonefos and Zometa groups. However, the rate of osteonecrosis of the jaw, a condition in which there is a loss of blood supply to the jaw resulting in jawbone death, was higher in the Zometa group (3.5 percent) compared to the Bonefos group (0.3 percent).
During his presentation, Dr. Morgan posited an important question regarding Zometa’s effectiveness in improving survival: “Is the [survival benefit] because of an anti-myeloma effect or because of the effect of reducing skeletal-related events?”
Analysis of the results showed that there was no relationship between a reduction in skeletal-related events and patient survival. Additionally, patients without myeloma bone disease experienced a survival benefit when treated with Zometa. Therefore, it was concluded that Zometa must have inherent anti-cancer effects of its own…
There’s a glitch in my blogging platform; I have trouble maintaining a link to Myeloma Beacon articles for very long. But if you would like to read the rest of the article, copy and paste this into your browser:
Like a lot of drugs used to treat less common diseases, once a determination was made that Zometa helped improve things, research was cut back. Its hard to find much data post 2010.
The stats above highlight my indifference toward bisphosphonates in general. Yes, there is a clear benefit; albeit relatively small. Fortunately, the risk of ONJ has dropped even lower than 3.5% now that physicians are more experienced administering Zometa.
From time to time there’s talk about new, more effective Zometa substitutes. But much of that research seems to have stalled. My theory: there isn’t as much money in it as there is in developing a drug like carfilzomib or panobinostat.
It’s always dangerous to start a medically related statement, “If I were you…” But to avoid misunderstandings, I’m going to do it anyway. If I were a newly diagnosed multiple myeloma patient with some evidence of bone involvement, I would allow my doctor to administer Zometa monthly, without reservation, for the first two years.
After that? What if your bones aren’t damaged? That’s a conversation to have with your doctor(s). Most will insist you take it at first, bone involvement or not. But at the two year mark, cutting back to every two or three months probably makes sense. Why risk complications for a diminishing rate of return?
The International Myeloma Foundation (IMF) site features a lot of information about bisphosphonates and Zometa. Here’s a link to International Myeloma Working Group (IMWG) guidelines about it:
My guess is your doctor may not have read it and may or may not agree with some of the guidelines.
The bottom line: compared to a lot of the drugs we use post diagnosis, Zometa is pretty low on the risk list. But that doesn’t mean you should blindly take it–or any drug–without understanding why.
When I relapsed the last time, my specialist at Mayo recommended I start taking it monthly again. I thought, “Why not?” I had new bone damage. Up to that point, I had been getting Zometa infusions sporadically; moving allowed me to skip a number of quarterly infusions.
From everything I’ve heard, Zometa has an amazing half life. Once it’s built up in your system, it can continue working for years. So when Dr. Tricot in Iowa recommended I wait to use it until sometime after my stem cell transplant this summer, I jumped at it. I haven’t had an infusion now for four months.
Please don’t hesitate to email me with any of your myeloma related questions; I answer dozens best I can every day. You aren’t imposing. I want to help anyway I can. My email: [email protected]
Feel good and keep smiling! Pat