JNF said...
One issue in front of the reimbursement guidance process is the negative side effect some people have regarding salivary and tearing function. The injectable has a way of concentrating in these areas and can cause damage degrading their function resulting in dry mouth and/or dry eye. I don’t remember these were observed in the two trials but has been reported in other PSMA studies. There is good commentary about this on the PCF website. CMS and third party payors will be very careful with this as they don’t want to potentially have to pay money treating side effects of the scan and injectable. …………….
Jerry L. said...
JNF...............................
I am aware of the salivary and tearing risk…My doc said that they might be able to ice those areas so they are not impacted as much…I think I also saw an article/video about that…I’m going to have to find that…somehow, I think I have time to locate it.
JNF, do you have a link for that discussion at PCF? If it is different from the one I am linking to below?
So are the salivary and tear SEs for the scan to locate PC cells, or for TREATMENT using these carriers/ligands, or both? If the SEs were very common, losing the ability to make tears and/or saliva would be a high price to pay to find my PC mets. It might be worth it, depending, but that would be a high price.
https://www.pcf.org/c/targeting-psma-part-4/"So, with all this published success, is there a downside to radioligands? Just like the use of magic in fairy tales – they come with a price. The radioligands target the salivary glands, where there is a small amount of PSMA produced. Beta particles such as Lu177, as used in the Novartis compound, generally cause only minor salivary gland toxicity. But, “since alpha particles are at least 1,000 times more potent than beta particles,” says Bander, “when you put the alpha particle on the ligand, it targets the salivary glands and the tear glands, and they get destroyed.” Now, you might be thinking, losing my salivary glands is a small price to pay for progress against prostate cancer. But Bander would suggest that you think very carefully about
this. “When you destroy the salivary glands, the result is absence of saliva, a persistently dry mouth, inability to taste, difficulty swallowing, and tooth decay and loss. Affected patients report that it’s a pretty miserable existence. So that has proven to be a major impediment to using the small ligands to target the alpha particles: even though you can get promising tumor responses with the alpha particle, it can be intolerable for the patient.”
Is there any way to avoid the salivary gland toxicity? As it turns out, there is. “While the small molecule ligand targets the salivary and lacrimal (tear) glands, antibodies do not,” says Bander. “Antibodies are much larger molecules than the ligands.” With the small ligands, the radioisotope “can easily pass through normal tissue barriers. But, when you deliver the radioisotope by use of the antibody, we see no targeting of the salivary or lacrimal glands.”
In fact, “we recently completed a trial at Weill Cornell using our J591 antibody to target the alpha particle, Ac225. Based on an interim analysis, we have seen minor salivary gland toxicity in 6 of 27 patients, 5 of whom had previously been treated with the small ligand. We found that the antibody-targeted alpha particle was well tolerated and very effective against the prostate cancer, even in patients who had previously progressed after treatment with the ligand-Lu177.” This is a PCF-funded phase 1 trial.
Another key difference between the antibody and ligand: “The ligand is excreted from the body through the kidney and bladder,” says Bander, and there is a risk of kidney toxicity. “It has not yet been a significant problem, although there have been a few reports of kidney toxicity from the ligand with an alpha particle on it, and it may take a while to develop. With the antibody, the path of excretion is through the liver, so the kidney is less likely to be subject to damage from the alpha particle. The liver is pretty resistant to radiation.” ................"