I think the other key finding at ASCO that really informs that question is the finding from the group in Australia on the higher rates of clonal hematopoiesis that were observed in a study comparing lutetium with cabazitaxel. And so what they did observe is that CHIP mutations, and these are precursor mutations to myelodysplasia or leukemia, these are actually found pretty commonly in prostate cancer patients...
I think the other key finding at ASCO that really informs that question is the finding from the group in Australia on the higher rates of clonal hematopoiesis that were observed in a study comparing lutetium with cabazitaxel. And so what they did observe is that CHIP mutations, and these are precursor mutations to myelodysplasia or leukemia, these are actually found pretty commonly in prostate cancer patients. And that’s likely true across multiple solid tumor types as the importance of clonal hematopoiesis is being increasingly recognized. But what was surprising about that abstract was that the rates of clonal hematopoiesis go up significantly after lutetium and much more so compared to cabazitaxel chemotherapy. And so that abstract, that finding, which was really great work from the investigators, it becomes even more important now when we’re considering the prospect of using lutetium as a true first line in hormone-sensitive metastatic prostate cancer, where patients live years and years, thankfully. Well, that means more and more potential for those clonal hematopoiesis mutations to cause clinically manifest bone marrow disorders. So that’s an important area and that means that we’re going to have to be really careful about patient selection and really identifying the patients that are most likely to benefit from early incorporation of lutetium. I think that that also means that we have to be careful about using lutetium earlier as a means of delaying hormone therapy. There was another abstract called the BULLSEYE trial, which came out of the Netherlands, which used lutetium as a standalone for patients with oligometastatic hormone-sensitive prostate cancer, which is an attractive strategy in the sense that it delays hormonal therapy, which we know causes a lot of side effects. But when we have to take into account the prospect of increased rates of clonal hematopoiesis, I’m not sure that that risk-benefit actually is so clear in favor of lutetium. So I think that’s really important. You know, obviously there’s a wave of new radioligand therapies like alpha emitters, actinium, lead, terbium, which were presented. I think right now we’re still waiting to see whether there’s true differences in durability and true improvements there relative to lutetium, which I think right now is still premature. And it’s going to be important because again high-risk prostate cancer in the metastatic setting is at this point looks to be very much in a post-lutetium setting and so we have to be careful about using too many bone marrow targeted agents that deplete the bone marrow in the wider landscape of prostate cancer management.
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