ICML 2025 | Comparing consolidation options in CNS lymphoma: autoSCT & reduced-dose whole-brain radiation

So, the treatment paradigm for primary CNS lymphoma includes an induction with high-dose methotrexate-containing regimens, and then that’s typically followed by consolidation in patients who have a response to induction. You know, I put all this together for ICML, so I’ve looked at all the data. There’s lots of prospective data really comparing these different consolidation regimens, and it boils down to autologous stem cell transplantation, whole brain radiation therapy with non-myeloablative chemotherapy, or non-myeloablative chemotherapy without the radiation. And when we look at the prospective data over the years, autologous stem cell transplant has been shown to be better than doing non-myeloablative chemotherapy in terms of more durable control. When you compare it to whole brain radiation, and as a radiation oncologist, I really want to specify that we’re talking about what I’ll call standard dose whole brain radiation, which means doses higher than 30 gray, so typically closer to the order of 40 gray. We see that depending on which study you looked at, it looks like stem cell transplant likely has more durable control than whole brain radiation at standard doses, but the toxicity profile is a little bit different. And some studies have shown similar, I mean, similar survivals, but really just durable control with transplant. But the toxicities are really where they differ. And so for transplant, we do see a handful of transplant-associated mortalities. And so patients typically, we think about them needing to be fit, younger. And then with standard dose whole brain radiation, the concern is really neurotoxicity. So based on clinical outcomes, and also looking at MRIs, we see greater neurotoxicity with standard dose whole brain. So as a radiation oncologist, I also wanted to specify that dose because I’m excited about this shift towards reduced dose whole brain radiation, which is more on the order of 23.4, 24 gray. So almost half of what historically had been used. There’s a prospective RTOG trial. The preliminary data was published a few years ago back at ASCO in 2020 that showed very promising results with no increased neurotoxicity with reduced dose whole brain compared to non-myeloablative chemotherapy alone and showed better progression-free survival. So what I did with my group at Sloan Kettering is we actually looked at a huge cohort of patients who had from the 80s until now, basically, to compare these different consolidation regimens. And this was published in Blood Advances last year. And what we saw was, first of all, any consolidation is better than none. So that’s important to know. When you account for all clinical demographic variables, there’s no significant difference in progression-free/overall survival with these different consolidation regimens, which I think just speaks to the fact that it’s all about patient selection. So for fitter patients, you know, again, younger or fitter older patients, really transplant seems to have some of the best durable control over time. But then, you know, right next to it, we have reduced dose whole brain radiation. And while this is retrospective data, there are no prospective trials comparing this reduced dose whole brain to transplant. So I think that this study that we did really encourages us to think about using reduced dose whole brain radiation in patients who cannot get transplant. So we basically support that prospective RTOG data showing that reduced dose whole brain likely is preferred to non-myeloablative chemotherapy. So I think that those are the main take-homes when we’re thinking about different consolidation regimens for patients who have a response to methotrexate-containing induction.

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