EHA 2024 | Final long-term follow-up results of the RELAZA2 study: MRD-guided treatment with aza in MDS and AML

So it’s a great pleasure to present the results today at the EHA meeting here in Madrid, on behalf of all my coworkers from the Study Alliance Leukemia. In RELAZA2, we investigated azacitidine in measurable residual disease-positive patients with MDS and AML after conventional chemotherapy or allogeneic stem cell transplantation. And of course, we only included patients in CR or CRI. We did a regular MRD assessment every 3 to 4 weeks at the beginning, and if patients turned MRD-positive we treated them with aza for the first six months and then we did a first response assessment. If they responded, we decreased the dose a little bit and if they didn’t respond, we increased it. And at the end, patients were treated for up to two years. 

And today, I’m very happy to present the long-term follow-up results, it’s now a median of about 23 months. We followed up our patients, and we can say that from the initial response perspective, 65% of included patients and treated patients responded to aza. We divided it into major and minor response. Major means that they already turned MRD-negative after aza and minor MRD response means they are still MRD positive, but didn’t have a relapse and also no clearance of MRD. And we could show that, especially in relapse-free survival and overall survival, major MRD responders are superior. They had a significantly better outcome compared to non-responding patients. And also in contrast, especially in a relapse-free survival setting, compared to patients with only a minor response. And we could also say that during our long-term follow-up in major responders, it was about 28 months, that more than half of our patients with an initial response sustained this response without any hematological relapse. They stayed alive. And we were also able to show that they were able to stop aza treatment. And in the median, it has been around 20.8 months without any treatment, and they are still in hematological remission. 

And therefore this is also our conclusion. We can say that RELAZA2 shows, also in the long-term follow-up perspective. that it is safe and it’s able to delay hematological relapse. And if patients respond, we see some long term responses. And we were also able to identify some biomarkers of response like lower MRD at the beginning, long time from last treatment, and also favorable ELN risk. These were some predictors with a better outcome and MRD response after azacitidine. We did not only show that we have some long-term responders, we were also able to show if patients initially respond to aza but then again, had the relapse, we were able to show that azacitidine treatment was able to delay this hematological relapse for around a median of 13 months. And it’s also important, of course, to have a look into MRD-negative patients. And our long-term follow-up also provided some data about these patients. So patients having a complete MRD-negative course without the appearance of MRD, they had the best outcome compared to our MRD-positive patients in regard to relapse-free survival and overall survival.