What is Off-label Use of a Drug?

What is off label use of a drug?

So off label use of a drug is when we use a drug that's FDA approved for a different indication or a different condition for something that it wasn't originally approved for.

really good example of this would be a drug like venetoclax.

So for example, venetoclax is FDA approved for certain types of lymphomas.

Now, even for certain types of leukemias, not yet approved for any multiple myeloma indication. But we do see that there is activity of venetoclax in patients in particular who have a translocation 11;14. oftentimes we will use venetoclax off label to treat patients who have that mutation.

it doesn't mean that it's a data free zone. We definitely have data that supports this. It's just not an FDA approved indication. Some of the challenges of off label drug use is really getting it approved by insurance. So a lot of times because it's not FDA approved, the insurance may not give prior authorization or not want to pay for it.

So oftentimes it requires your physician to have to appeal, go under, undergo kind of an appeal, process your insurance. Sometimes we have to set up a phone call with the insurance company to justify why we need to use it and oftentimes are able to kind of get it. If we go those steps,

very, very, very few combinations in use right now for myeloma are actually FDA approved for use in and so which is you know, interestingly enough, if you're looking at quadruplets regimens that are currently approved for use Melphalan, bortezomib, prednisone, and daratumumab is FDA approved.

Now, I think you would say very, very few if any patients in the U.S. are getting that. So most of the time, once a drug has been established and a combination has been

published, then there's there's usually less pushback from the FDA and it ends up being sort of a manpower thing, too. I mean, they're usually they're looking to help get new drugs, new options out there, and then sort of leaving it up, I guess if you will.

And this is not just true in myeloma. This is true in all sorts of other cancers, to let then the research organizations come up with combinations that sort of make sense, if you will. But but very few drugs are actually used for the purpose that led to their initial approval. And that's not just myeloma. That is across the board in cancer treatment.

there is a drug that is used in many, many, many types of cancer called cyclophosphamide. And that's a drug that goes back to the 1950s and that drug approval. And I'm going to probably I believe it is approved for use in lymphoma, but it is used in breast cancer treatment.

It is used in myeloma. It is used in Hodgkin lymphoma. It is used in all sorts of lymphomas. You name it. It's used actually as a treatment for not cancer. It's used in kidney problems, it's used in lupus. It was never approved for that by the FDA. But the idea is that now you have legitimate, scientifically vetted or what people say sometimes is peer reviewed, meaning that objective science is outside of the research, look at it and say this is legitimate, but this is considered, very reasonable.

And what the FDA also does, which is actually very important, they also do what's called post-marketing monitoring. So, for example, this recently happened to a myeloma drug, Melflufen for example. And so Melflufen was approved for use in the U.S. This is a drug that is kind of a reworking of Melphalan. And it was used it was approved for patients who have had more than three lines of therapy.

But in the middle or shortly after Melflufen was introduced, another study came out showing that there were some serious toxicity concerns. And so looking at those and looking at sort of the general atmosphere of what was going on in myeloma treatment, the FDA decided to pull its approval.

so they do do that in medications. And that's happened for other drugs in other types of cancer as well, where a drug either is completely taken off the market or it loses or the FDA specifically comes out and says, we're not recommending this drug for use for this type of cancer.

one of the things that can happen in cancer care that I think is not a good plan of attack, is that you can sometimes do what people would term deductive reasoning and saying, you know, if this drug A has done so well with B, I bet you if you throw in D, it's going to be even better.

And even though that can sound very logical sometimes, that's a terrible idea.

So what we do try to do with the NCCN guidelines is basically use best quality evidence but rate it. So for example, if this is what if combination A was tested against B, A is clearly better, that's considered evidence level A like the best evidence.

Now if you have a combination in patients who had very few treatments, no options and you did a small study, maybe under 100 patients and published those results, that would likely get you a recommendation of 2A.

so clearly a step below but still available. And we know from experience, and the NCCN actually chart tracks this, that typically a regimen that is published in the NCCN will be covered by insurance.

And they're very mindful, I think, of their role. And so they don't want to just frivolously put something on the guidelines and, you know, request come in all the time from entities to say, please put my drug on for this indication. And I think the NCCN does a very good job as saying until you show us some really, you know, reproducible data we're not going to do that