ASH 2023 | GvHD prophylaxis in AML: PTCy versus CNI
Arnon Nagler, MD, Chaim Sheba Medical Center, Tel-Aviv, Israel, discusses a study comparing post-transplant cyclophosphamide (PTCy) to calcineurin inhibitor (CNI)-based graft-versus-host disease (GvHD) prophylaxis following allogeneic stem cell transplantation (alloSCT) in the treatment of acute myeloid leukemia (AML). The findings reveal comparable overall survival (OS), with a lower rate of GvHD in the PTCy arm, which did not jeopardize the graft-versus-leukemia (GvL) effect. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
So I just presented today in the oral abstract in which we looked on the relapse rate in unrelated, transplanted received post-transplant cyclophosphamide. And the question there is, because we know that post-transplant cyclophosphamide changes the biology of the disease by upregulating T regulatory cells and knocking down the T-cells and cytokine production, increasing the expression of PD1 on T regulatory cells and also knocking down the NK mature, NK cell donor mature and NK cells...
So I just presented today in the oral abstract in which we looked on the relapse rate in unrelated, transplanted received post-transplant cyclophosphamide. And the question there is, because we know that post-transplant cyclophosphamide changes the biology of the disease by upregulating T regulatory cells and knocking down the T-cells and cytokine production, increasing the expression of PD1 on T regulatory cells and also knocking down the NK mature, NK cell donor mature and NK cells. The question if post-transplant cyclo will increase the relapse rate post-transplantation because in patients that receive calcineurin-based inhibition of GvHD, there is correlation between GvHD and GvL, so if we reduce the GvHD and maybe we are reducing the GvL and then the relapse rate is higher.
So, in a more than 7000 transplant unrelated mismatch or match unrelated transplant, we looked on the relapse rate compared to a similar transplant that received a calcineurin inhibitor-based anti-GvHD prophylaxis, and we did not find increased relapse rate in the patients that received post-transplant cyclophosphamide. And what we observed is reduction in non-relapse mortality reduction in GvHD with PTCy, improvement in the composite endpoint of GvHD, relapse-free survival, while leukemia-free survival and overall survival was not changed.
So post transplant cyclo in the unrelated setting does not jeopardize the graft versus leukemia effect and doesn’t result in increased relapse rate. And the reason for this is that there is a different signature of the T-cells and the cytokine production in the patients who receive PTCy. So they knocked out the T-cells that are alloreactive T-cells that are responsible for the GvHD, but the CD8 cells are not jeopardized. And then they can mediate the graft versus leukemia effect. And in patients that receive a PTCy, there is no direct correlation between GvHD and GvL. So there is a separation between the graft versus leukemia and graft versus host disease.
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