umbralisib

[beanlake14]

I know I have posted before about being in the Phase II trial with the drugs ublituximab, umbralisib, and 2 years of venetoclax. Again, the trial was suspended because there was no benefit seen on the arm using umbralisib. I am still on the drug because I am tolerating it well, and my numbers are good. Of course, the long term effects of a drug that will now not be approved by the FDA is a little disconcerting. I am just wonderin if anyone on here is also pushing forward with staying on the drug. As I have stated previously, my dr can't figure out if I am doing well in spite of the drug or because of it. Any one else still on umbralisib?

[AussieNeil Administrator]

It's not that there's no benefit, it was safety concerns that led to TG Therapeutics suspending the CLL clinical trial:

medicalnewstoday.com/articl...

PI3K-delta drugs do work, it's just that this class of drugs comes with what's considered an unacceptable risk of toxicities, with lung infections a significant concern, along with transaminitis (liver toxicity). The first in class PI3K-delta drug idelalisib, didn't achieve approval for first line therapy in the USA many years ago, but it did elsewhere, e.g. Europe:

pubmed.ncbi.nlm.nih.gov/256...

ashpublications.org/blood/a...

You may remember Chris/CLLCanada couldn't tolerate ibrutinib, but did well on idelalisib.

There have been voluntary withdrawals of idelalisib this year, now that we have what are considered safer treatment drugs.

federalregister.gov/documen...

lymphomahub.com/medical-inf...

Provided your specialist keeps an eye on your liver function tests and your lung health and you take particular care to have any respiratory infections you develop carefully monitored, you may find that you'll continue to do well on umbralisib for many, many years.

Neil

[beanlake14 in reply to AussieNeil]

Than k you. Just so hard knowing what to do.

[AussieNeil Administrator in reply to beanlake14]

You are in an awkward situation, but unlike the many patients who were treated with idelalisib after it was approved, you do have the advantage of being carefully monitored in the umbralisib clinical trial. You are also aware of the risks that have been identified through the early trial assessment. Your other advantage is that this gives you a period of control of your CLL with a drug not generally available. That improves your chance of staying ahead of changes in your CLL. I don't think you've been treated with a BTKi drug yet, plus other treatments are continually being developed. (it might be a good time to update your bio with your treatment history healthunlocked.com/profile/...

Please do discuss your concerns with your specialist about the recently identified risks with umbralisib and if you aren't satisfied that your health is being adequately monitored, check if you have a better alternative available to you.

Neil

[curlscurls]

I was on Umbralisib from April last year through December.

From mid August through September I was on prednisone because of extremely high liver enzymes. They came down pretty quickly but the prednisone was tapered and the dosage was switched to 3/4.

I have smzl not cll, so the goal is shrinking the spleen. My accounts aren't particularly bad. (Smzl is another indolent marginal zone lymphoma. Mostly it affects the spleen and shows up in the bone marrow, but other nodes aren't enlarged. It's a little different than CLL and usually expresses CD 20 bright so the first line treatments are the CD 20 drugs such as rituxan.)

It definitely, a little bit, kept the spleen from growing. It didn't shrink it. It might have on the full dose but we didn't do a test at that point and when I stopped in December it was the same size as when I started.

I was on a washout period before the next drug and during that month my spleen grew so it was definite that the Umbralisib was helping. My spleen grew quickly and substantially so I went from bloated to having trouble breathing, in less than a month. I was told that stopping these medications suddenly can create a quick increase like that.

I was not comfortable with the side effects. There was muscular discomfort. And something with my vision. I was worried enough to go to a retina specialist who said there's no damage. Prednisone is known to cause long-term eye issues. But Umbralisib causes eye damage in fetuses. It isn't known to in adults, but it hasn't been rigorously tested. But when I was off, I was glad I was off as both symptoms went away. Looks like my blood pressure was high on it too.

That was my experience.

It takes a while to start working, so the doctor was reluctant to take me off of it and try something else and then try it again. I have two bottles sitting in my closet that I don't know what to do with.

Curiously, my doctor was supposed to testify on behalf of Umbralisib. His and other doctors' point is that the claims of increased death are flawed because the arm with umbralisib was started during covid and the other arm had started before covid. Or something like that. So the increased deaths was probably an environmental factor. So it is possible that the drug will get reassessed and brought back on the market.

The other two drugs in that study have a good chance of working, so it's hard to know if the Umbralisib is adding anything.

Ideally is if there's a way to go off of it and see if was contributing. Have you asked the company their policy on distributing it if it's working for you?

There's a Medicare law that if you've been on a drug in the last year and it's in a protected class which includes the Cancer drugs, then an insurance company is obligated to approve it. However that probably doesn't apply when it's not FDA approved.

Venetaclax, to my understanding is now taken for about 2 years. Maybe finish off the 2 years of that and whatever the time frame of the study was with all three drugs. And then when you stop see how it goes. Of course if it turns out that the other two weren't enough it'd be very hard to get a hold of Umbralisib. The company could answer the availability question.

However there are other treatments coming. I've got my eye on BiTE, which should be available in the next year.

I'm currently in a study using rituxin, revlimid and tafasitamab. The Revlimid is supposed to be hard to take. I'm doing okay with it. This particular combination is for follicular and they're trying it a marginal zone. But the tafasitamab is interesting. Because it's worked very well in diffuse large cell lymphoma. And they're first trying it in indolent conditions. It's a CD 19 not a CD 20.

That really is a tough question that you're facing. As I've written this, I haven't come up with a good solution. I hope your doctor has more information and ideas. And that your instinct points you in a direction!!

[beanlake14 in reply to curlscurls]

Your reply give me pause because I just suffered a detached retina and had eye surgery. My eye doctor said the problem had to be coming on for a time, but it hadn't. It was sudden. I wondered at the time if there was a connection to the drug, now I am more concerned. My oncologist didn't think there was one. I have no side effects from umbralisib, but still worry what's happening that I do't know up and will suddenly show up. If I go off, I'm concerned the leukemia will make its' way back. But you have given me pause enough that I am going to push to see if this is what happened to my eye.

[curlscurls in reply to beanlake14]

I was aware of it impacting my vision. So that's different. From the start, I pointed it out. I also had vision changes on Zanubrutinib, and something on the study I'm on is doing something too.

The retina specialist was sure it hadn't injured the structures in my eye. So there is that. Be good and interesting to hear what yours says about the med.

Also at the least, it's worth reporting the coincidental (or not) detachment to TGtheraputics so if there's a pattern across people, it shows up.

[Smakwater in reply to curlscurls]

Treatment with Venclexta is recommended for 12 months - venclexta.com/previously-un...

JM

[NYCBill]

Beanlake. I recently completed that trial after 2 1/2 years, stopping twice for problems. The news of FDA withdrawing clearance came a few months before I was due to stop. I was already in remission. I learned of the FDA rethink on a CLL site, and asked my doctor. He said to soldier because it helped me, and held the line after the FDA ruling. So, being either hopeful or fatalistic (I’d gone through a lot and wanted to get done to get done—plus there was no smoking gun in the study results) I completed it a little while ago. I do feel better off the strong medication (side effects appearing to come along with many of these CLL drug regimens), and appreciate that humbly. That’s my experience. Best of luck. Bill

[beanlake14 in reply to NYCBill]

Thank you. I guess my issue is for some reason, my oncologist wants me to stay on umbralisib until I relapse. Since I am doing so well, we can't tell if it was the 3 drug combo I finished a year ago, or the continued use of umbralisib. So, that's my dilemma. Never going off umbralisib until I relapse unless I decide to myself.

[NYCBill]

I understand now. It is a dilemma. It’s somewhat similar to what mine was—only you’ve got an open-ended duration. … A second or third opinion may be worthwhile to give you more information and potentially settle your mind and decision. I began looking for another cll expert to consult, but ultimately did not. … These are rough decisions at best of times and my heart is with you.

[beanlake14 in reply to NYCBill]

Great idea; thank you.