When will acyclovir be prescribed?

When will acyclovir be prescribed?

Acyclovir is an antiviral drug that is used very commonly in multiple myeloma. In fact, I often coin it as this is a vitamin for multiple myeloma patients because whenever they're on drugs such as proteasome inhibitors, ixazomib, bortezomib, Velcade or carfilzomib and daratumumab, elotuzumab, or now with even the immunotherapies, they are at risk of reactivating herpes zoster or shingles. We prescribe it at the newly diagnosed setting or relapse setting. Whenever patients are on these drugs, they need to be on it. Even in the transplant setting, once the patients are through the transplant, they transition to their maintenance therapy, oftentimes which is done with Revlimid. They continue the acyclovir prophylaxis for at least one year after their transplant. So that's commonly what we do, and we continue with all these other therapies nowadays, even with CAR T-cell therapy. The doses are adjusted based on their kidney function. Usually it's 400mg twice daily and then that can be reduced
based on their kidney function.

So, acyclovir is a drug that's designed to prevent viral reactivation. So when we're younger, we're all exposed to various viruses and we either get through them through natural immunity, or maybe we've been vaccinated against them so we have a silent infection, but these viruses will stay in our bodies in certain areas for the rest of our lives and our body is able to keep them under control so that they don't have any subsequent manifestations.However, when you're on treatment for things like multiple myeloma, many of the drugs will suppress the immune system, remembering that myeloma is a cancer of your immune system, so treating it with immunosuppressive medicine is very effective, but it also has some effects on the healthy immune cells. And in situations like that, you are at risk of viral reactivation for these types of things that exist in our body silently for the remainder of our lives in general. So these are things like shingles, HSV, things like that. So, acyclovir is very helpful in preventing those from occurring. The traditional dose is 400mg twice a day, but that can be adjusted based on a patient's renal function because it is cleared through the kidney’s system. So sometimes we do have to adjust it down a little bit if their renal function isn't quite, you know, at baseline, that kind of thing. But in general it's a very safe drug, it has very little toxicity. Most patients tolerate it really well, and, you know, I think most people are on that for quite a long time because most myeloma therapies do predispose you to an increased risk of viral reactivation.

Will the patient still need to take acyclovir if they've had the shingles vaccine?

So the SHINGRIX vaccine is normally a pretty effective way to prevent the VZV virus or the varicella virus, which causes shingles, from reactivating. The vaccine is designed to stimulate the immune system to sort of help it keep that in check, again, for patients who may have had a little bit of waning of their immunity as they get older in life, that's pretty common. Unfortunately, with myeloma patients, that's not going to be enough when they're on the types of therapies that suppress the immune system. So they still are at risk for shingles reactivation. So acyclovir really is the gold standard in that case. Certainly is worthwhile to be vaccinated against it. You know, to get the SHINGRIX vaccine. I certainly recommend that in all my patients. But it's not enough when you're on certain treatments to just be on that. If you are able to be on some of the therapies that don't require that, then by all means, the SHINGRIX vaccine is enough.

It's a very important question that my patients ask me. “Hey Doc, I got the shingles vaccine. Can you please discontinue acyclovir?” I believe that I’m not that cavalier yet, where I discontinue their prophylaxis. I still continue it.

Why will the shingles virus be reactivated in myeloma patients on certain therapies?

We are exposed to many viruses throughout our lifetime. So if our immune systems are not compromised, we have no concerns of those viruses reactivating again and causing problems. However, multiple myeloma is a disease where the immune system becomes slightly dysfunctional as a result of the disease, but also the drugs make it dysfunctional. And then there's a chance, because the herpes zoster virus can lay dormant there for a long time. And when your immune system is suppressed, it can get reactivated again. So that's usually what happens, and that's why there's a huge concern.

Is acyclovir prescribed after CAR T-cell therapy?

So when you take a CAR-T, one of the keys to remember for the myeloma CAR-Ts is that they don't just hit myeloma cells. The target of myeloma CAR-Ts, in general, it's either going to be BCMA or GPRC5D. The GPRC5D CAR-Ts are not commercially available yet. They're only available in the context of a clinical trial. But in both of these instances, these markers exist not just on transformed plasma cells,which are what myeloma cells are, but they're on normal plasma cells as well. So the CAR-Ts will attack the healthy plasma cells to a large extent as well as the myeloma cells. and that will suppress your immune system. And, before CAR-T, most patients will get lymphodepleting chemotherapy, which will also suppress your immune system. So all those patients should absolutely be on acyclovir to help prevent shingles from reactivating. Now the question of duration, that's sort of an open-ended question. I check levels in my patients,  at least monthly for the first six months. And then when I start to see that they're having recovery of their healthy plasma cells, I'll revaccinate them against shingles. And then, at that point we can talk about coming off acyclovir, but usually I'll leave them on for approximately a year post-CAR-T.

Are there any therapies in myeloma that you might not need to take acyclovir with?

Yeah. So the IMiDs specifically, if you're on IMiD monotherapy, that is not so suppressive that you’ll need to be on shingles prophylaxis. Now a lot of times people will be on IMiD monotherapy after a transplant, and at that point, you're still immunocompromised from the transplant and you're still recovering your immune system from the transplant-related cell killing. There will come a time after transplant if you're on just, you know, lenalidomide or pomalidomide where you can come off of acyclovir.