The Precision Team in AML

Co-Chairs, Naval Daver, MD, and Joseph D. Khoury, MD, FCAP, discuss acute myeloid leukemia in this CME/CC activity titled “The Precision Team in AML: Exploring Pathologist-Informed Clinical Decisions in Challenging AML Settings.” For the full presentation, downloadable Practice Aid, slides, and complete CME/CC information, and to apply for credit, please visit us at PeerView.com/XSA865. CME/CC credit will be available until April 13, 2024.

Prof Robin Foa speaks to ecancer at the 2019 European Hematology Association (EHA) Annual Meeting about treatment alternatives to chemotherapy for leukaemia.

He explains that today there are many targeted treatments that are succesful, particularly with the help of minimal residual disease monitoring.

Prof Foa also highlights CAR-T as an area of excitement and a real step forward but that the treatments high cost and restricted availability are current setbacks.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

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Hagop M. Kantarjian, MD of MD Anderson Cancer Center, Houston, TX gives an overview of developments in therapies for acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. Prof. Kantarjian explains that we are in a revolutionary period for both acute lymphoblastic leukemia (ALL) and AML and we will see changes in how we treat and cure these diseases. In AML, we have reached a limit in terms of curing the disease with chemotherapy combinations such as 7+3 or the more intensive FLAG-Ida using high-dose cytarabine (Ara-C). Many targeted therapies as well as immunomodulatory strategies are available now. AML cells express CD33 and CD123 and monoclonal antibodies conjugated to toxins and antibody constructs can target these surface proteins. Further, patients may have FLT3, IDH1 or IHD2 abnormalities and inhibitors are available for these mutations. He further discusses the development of BCL-2 inhibitors, such as venetoclax (ABT-199), which in combination with epigenetic therapy or intensive chemotherapy shows promising results. In terms of the microenvironment, checkpoint inhibitors have also been shown to be active in hematologic malignancies. Further, there are new modified chemotherapy agents such as CPX-351 and vosaroxin, which may improve our ability to give chemotherapy more effectively. In conclusion, there are now several agents available and Prof. Kantarjian believes that their development will lead to an improvement in the cure rate of AML.

Joshua F. Zeidner, MD, will discuss the evolving diagnostic algorithm for AML-MRC, prognosis, treatment outcomes, and unmet needs.

Firas El Chaer, MD, University of Virginia, Charlottesville, VA, discusses the role of post-transplant maintenance therapy in acute myeloid leukemia (AML), highlighting data from key clinical trials including SORMAIN (EudraCT 2010-018539-16), RADIUS (NCT01883362), and BMT 1506. Whilst the SORMAIN trial showed a significant benefit in overall survival (OS) for patients with FLT3+ AML treated with sorafenib maintenance, the RADIUS trial did not report any improvements for patients treated with midostaurin. Data from the BMT 1506 trial evaluating gilteritinib in the maintenance setting is eagerly awaited. Dr El Chaer also mentions a study assessing the use of azacitidine in the maintenance setting. According to Dr El Chaer, maintenance therapy remains important in certain patient groups, including patients with high-risk disease, patients who are measurable residual disease (MRD)-positive prior to stem cell transplantation, or patients treated with a reduced-intensity conditioning (RIC) regimen. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.

Erythroid and Megakaryoblastic leukemias are rare forms of acute myeloid leukemia, defined by increased blasts with either erythroid or megakaryocytic features. This presentation will discuss molecular and pathologic insights gained from cell culture and murine models of erythroid and megakaryoblastic leukemias. Our analysis has identified FOLR1 as a specific therapeutic target that is uniquely expressed in CBF2AT3/GLIS2 (CBF/GLIS) acute megakaryoblastic leukemia. FOLR1 specific CAR T-cells and Stro-002, a FOLR1 antibody drug conjugate effectively target AML cells with FOLR1 expression resulting in increased survival of CBF/GLIS AMKL xenograft mice. Stro-002 has also shown significant efficacy in limited human studies under compassionate use basis. After viewing this lecture, participants should be able to:

1. Understand basic differences between pediatric and adult AML.
2. Understand controversies regarding diagnosis and evaluation of erythroleukemia
3. Understand the diagnostic features of CBF/GLIS acute megakaryocytic leukemia

Keith Loeb, MD, PhD Associate Professor Translational Science and Therapeutics Division, Fred Hutch Cancer Center Department of Laboratory Medicine and Pathology, University of Washington

01/18/23