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EHA 2021 | Sorafenib maintenace improves outcomes for FLT3-ITD AML

Ali Bazarbachi, MD, American University of Beirut Medical Center, Beirut, Lebanon, discusses the next steps in improving outcomes for patients with acute leukemias who undergo stem cell transplantation (SCT). Dr Bazarbachi gives an overview of causes of treatment failure, including poor prognosis associated with relapse after allogeneic-SCT, and discusses the use of hypomethylating agents and tyrosine kinase inhibitors post-transplant to prevent relapse. Dr Bazarbachi also highlights the positive results of two recent prospective randomized trials of sorafenib for post-transplant maintenance for patients with FLT3-ITD acute myeloid leukemia (AML). For patients who do not have FLT3-ITD AML, current strategies rely on hypomethylating agents, sometimes in combination with venetoclax according to Dr Bazarbachi. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.

Transcript (edited for clarity)

Basically, when we look to the causes of treatment failure, relapse after allotransplant is the first cause of transplant failure and the first cause of mortality after allogenic transplants. So historically, transplant was considered as the last step of treatment, but in the last decade, particularly in the last years, a lot of research was done to prevent relapse after transplants. So, using mostly pharmacological post-transplant interventions as prophylactic or pre-emptive treatment to prevent hematologic relapse after transplant...

Basically, when we look to the causes of treatment failure, relapse after allotransplant is the first cause of transplant failure and the first cause of mortality after allogenic transplants. So historically, transplant was considered as the last step of treatment, but in the last decade, particularly in the last years, a lot of research was done to prevent relapse after transplants. So, using mostly pharmacological post-transplant interventions as prophylactic or pre-emptive treatment to prevent hematologic relapse after transplant.

So, in the setting of acute myeloid leukemia, the most frequently used agents are hypomethylating agents such as, as a azacitidine or decitabine and tyrosine kinase inhibitors, FLT3 Inhibitors, particularly for patients with FLT3-ITD AML.

And actually, what we have shown within the EBMT Acute Leukemia Working Party, and based on multiple retrospective, singular institution, multi-institution registry studies, as well as now, there are two reported prospective randomized trials is, that sorafenib maintenance after allotransplant, has changed the prognosis of this disease from a high-risk, poor prognosis, AML to a good-risk AML. So, with the treatment strategy including tyrosine kinase inhibitor, FLT3 Inhibitors, and such as midostaurin, with chemotherapy for induction consolidation, allotransplant, and post-transplant sorafenib. Currently, the overwhelming majority of patients with FLT3-ITD AML can be cured, and transforming this into a favorable-risk AML, similar to what the tyrosine kinase inhibitors have done for Philadelphia-positive ALL.

For patients without FLT3-ITD, the current treatment strategies to prevent relapse after transplant mostly rely on hypomethylating agents azacitidine and decitabine, sometimes combined with venetoclax. However, the data is quite encouraging, but less strong in that setting. And actually, recently in Hematologica, we reported the consensus guidelines and recommendation from the EBMT Acute Leukemia Working Party for FLT3 -ITD AML recommending post-transplant sorafenib maintenance for prevention of relapse.

Thank you for your attention.

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