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EBMT 2021 | EBMT 2021 highlights: haploidentical transplant, GvHD prophylaxis and CAR-T

Arnon Nagler, MD, MSc, Chaim Sheba Medical Center, Tel-Hashomer, Israel, discusses what he’s looking forward to at EBMT 2021, in particular highlighting updates in haploidentical transplant for acute lymphoblastic leukemia and acute myeloid leukemia, and developments in anti-GvHD (graft-versus-host disease) prophylaxis and chimeric antigen receptor T-cell (CAR-T) therapy for myeloma. This interview took place during the 47th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2021.

Transcript (edited for clarity)

We are looking forward for EBMT which is this time, for the second time, virtual. We hope the next meeting will be in person. EBMT is the biggest meeting of transplant in Europe, usually with 5-6,000 participant from 600 centers. So, a lot is happening in EBMT, major developments and advances, especially that now we can offer transplant to almost every patient we need, thanks to the haploidentical transplant...

We are looking forward for EBMT which is this time, for the second time, virtual. We hope the next meeting will be in person. EBMT is the biggest meeting of transplant in Europe, usually with 5-6,000 participant from 600 centers. So, a lot is happening in EBMT, major developments and advances, especially that now we can offer transplant to almost every patient we need, thanks to the haploidentical transplant. So, the number of haploidentical transplant in Europe are booming, and especially with post-transplant cyclophosphamide, that was primarily in Baltimore.

The post-transplant cyclo knockdown, the allo-active cells upregulate the T regulatory cells and induce tolerance, and they change the biology of the transplant, and the result of haploidentical transplant are really encouraging, both for AML and ALL. So, we are not depleting these days T-cells from the graft, like in the beginning of the era of haploidentical transplant, but do non-T-cell depleted transplant with post-transplant cyclo. And again, numbers are increasing and results are better.

So we published, I think few months ago, a paper in Lancet Haematology in which we show that the transplant-related mortality in three periods of five years each, from 2000 and something til 2015, the transplant-related mortality went down from 50-something percent to 20, 25%, and the overall survival improved. And the improving in the transplantation outcome is better in haploidentical transplant than in unrelated transplant or in mismatched-unrelated transplantation.

The other big development in transplantation is the fact that the post-transplant cyclo become very popular and very effective anti-GvHD prophylaxis. So, the GvHD prophylaxis usually is with calcineurin inhibitor and methotrexate. This was established in Seattle maybe 30 years ago, and nothing changed for many, many years. But it turns out to be that the post-transplant cyclos that we started in haploidentical transplant move to unrelated transplantation, mismatch unrelated transplantation and in sibling transplantation.

So we have a paper now last year from the Acute Leukemia Working Party in mismatched unrelated transplant, nine out of 10, with post-transplant cyclo compared to the conventional anti-GvHD prophylaxis, and the results were better with post-transplant cyclo. And this year I will present a paper on sibling transplantations, comparing post-transplant cyclo to the conventional cyclo-methotrexate, showing that with post-transplant cyclo, we have lower incidence of chronic GvHD. And chronic GvHD is really major obstacle in transplantation, causing a lot of morbidity and mortality, because you need to give the patient immunosuppression for long time, and they come down with invasive aspergillosis or other type of infection. And so, the post-transplant cyclo change the biology and reduce, change the biology of transplant and reduce the transplant-related mortality.

There are some data that the post-transplant cyclo knockdown for the first months post-transplant, the NK cells, especially the recipient NK cells, the donor NK cells. And indeed, it have to be confirmed, but there may be some increase in the relapse rate in the early period of transplantation.

There are many new drugs and new compound for GvHD that were presented during this EBMT, and a lot of new data on the importance of microbiome for transplantation, but also for CAR-T cells, so there is data now that the microbiome also affect or dictate the prognosis and the response to CAR-T cells; and also, the toxicity of CAR-T cell cytokine release syndrome. Obviously, many, many abstract on CAR-T cells, new CAR-T cells, new construct of CAR-T cells, CAR-T cells to the other diseases, and academic CAR-T cells from Spain that was approved and from others. A lot of CAR-T cells in myeloma, allogeneic CAR-T cells. So really, the field is really moving very fast, and we are looking forward for this EBMT and for the new and novel presentation and the new studies that will be presented there.

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