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Impact of TP53 Mutation Clearance Prior to Allo-SCT

<ѻý class="mpt-content-deck">— Study clarifies if clearance prior to transplantation could influence outcomes
MedpageToday

At the recent 2019 American Society of Hematology annual meeting, there were a number of presentations on targeted mutations, and one study out of Moffitt Cancer Center in Tampa, Florida, looked at the controversy regarding the on allogeneic stem cell transplantation outcomes.

In this exclusive ѻý video, study co-author , from Moffitt, discusses her findings.

Following is a transcript of her remarks:

We had the ability here and the pleasure of presenting our own data on TP53 mutation for AML [acute myeloid leukemia] and MDS [myelodysplastic syndromes], which is a very exciting topic and time in that space. As many are aware, Dr. [David] Sallman [at Moffitt] and Dr. [Thomas] Cluzeau, in France, had been working with the targeted agent APR-246, in the setting upfront. What we presented on, rather, was the impact of TP53 mutation after transplantation, which is still a space where there's a lot of questions.

TP53 mutation after allogeneic stem cell transplantation -- the data is very interesting in that space. What we do know is that for those patients that do harbor this mutation, allogeneic transplant remains the only potential curative therapy available. However, the outcomes are very dismal, with overall survival at 2 to 3 years being 20% to 30% [reported] in the vast majority of papers, due to the vast majority of patients relapsing very early on after transplantation.

We wanted to look at if the clearance of TP53 mutation had any impact on outcomes after allogeneic transplant, and additionally if the type of conditioning regimen that is used for allogeneic transplant, be it MAC [myeloablative conditioning] or reduced-intensity non-myeloablative, made an impact.

There were several interesting findings from our work. One is that many of the patients were able to clear the TP53 mutation using hypomethylating agents prior to transplantation, and that has not been well described as of yet, so that was very encouraging to see. While it was not statistically significant, the use of hypomethylating agents versus intensive chemotherapy -- the results need to be validated in a larger cohort -- were very exciting and certainly did describe that it can be cleared using something like Vidaza [azacitidine] for treatment.

Additionally, what we did find is that clearance of the TP53 mutation versus those that retained the TP53 mutation ... there was very little difference, statistically insignificant impact, on survival, which I think is something that is up for debate and is something that was very interesting in the group right now and they're interested to hear about that.

What we did, however, find is that the conditioning regimen seemed to make an impact. Surprisingly, reduced-intensity conditioning and non-myeloablative conditioning versus those who received MAC or myeloablative conditioning, those patients had better outcomes. Those that received myeloablative conditioning actually had a worse overall survival, which I think was very surprising for the group to see.

We did note that this is a dealer's choice. It was retrospective, so there are certainly limitations to our studies, and certainly we do recognize that there is bias such that physicians may want or opt to use myeloablative conditioning if they feel that a patient's disease status is very severe instead of doing the reduced-intensity sort of approach, but it was very exciting to see that we don't necessarily need to use a myeloablative approach in a patient population that, in general, is in their late 60s and early 70s.