LU177

[TWTJr]

Does anyone know what problems Novartis had in manufacturing LU177PSMA? The company asks that adverse events after use of LU177 be reported. What sort of adverse events might be expected?

[Tall_Allen]

There was a manufacturing problem last year. I think the issue this year was the delay in getting FDA approval for the NJ facility to produce enough Lu-177 to keep up with demand. Formerly, the NJ facility was only approved for manufacturing Lu-177 for clinical trials.

[TWTJr in reply to Tall_Allen]

Thank you Tall Allen. I had an adverse event after my last LU177 dose which was administered on 12/14/23. Four prior treatments had gone well, and uneventful. However, after the fifth treatment, the 1 hr post treatment MDR (measured dose rate) measured at 1 meter was 7 mrem/hr, a dose emission rate twice that of the prior 4 treatments, with all treatments using an administered dose of 195 mCi, at least recorded in my provided medical records. All four prior MDRs measured 3.5-5 mrem/hr. As I have noted on earlier posts, after this last Lu177 treatment, one where the measured dose emission rated (MDR) was 7 mrem/hr, I went into rather marked bone marrow and renal failure. I have reason to at least question why. Was the high 1 hour post injection MDR reflective on an excessive administered dose?? I have read about dissassociation problems that LU177-PSMA ligand may have when certain issues arise (variation of temperature, time, pressure). I am seeking greater depth of knowledge of what happened.

[Tall_Allen in reply to TWTJr]

That can happen with subsequent infusions because there is less PSMA-avid cancer for the beta emitter to attack. When there are fewer targets, there is more toxicity as the radioactivity hangs around and attacks healthy tissue (tumor sink effect).

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

[TWTJr in reply to Tall_Allen]

Thanks so very much for the references, and I suspect the sink effect may account for the event. Since my tumor load was low (PSA 0.13) at the time of the last treatment. it seems that the injected dose should have been adjusted downward, or at least considered. The references you provided suggest with low tumor load that dose adjustment might be appropriate.

[Ramp7]

I completed 6 infusions with LuPSMA177 at Dana Farber as part of a trial last year. My PSMA expression was over 95%, very high. Initially my PSA came down dramatically, 8.1 to 0.19. But then slowly climbed back up to 4. From side conversations, I heard some individuals dropped out of the study due to blood issues and rising PSA. This was not officially discussed.