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Therapeutic Update in AML: Genomic Assessment Is Key

By: Susan Reckling
Posted: Tuesday, October 20, 2020

According to Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, what makes the treatment of patients with acute myeloid leukemia (AML) so challenging is that it is such a biologically diverse malignancy. As a result, comprehensive genomic assessment, both at diagnosis and recurrence, plays a key role in the optimal selection of novel targeted therapies and emerging strategies. Dr. Wang reviewed such newer therapies—including inhibitors of FLT3 and IDH1/2—during the NCCN 2020 Virtual Annual Conference, highlights of which were published in JNCCN–Journal of the National Comprehensive Cancer Network.

“Many of the novel drugs are specifically tailored for AML biology, and it makes sense to wait for genomic testing results,” she advised. “Clinicians need to be aware of what the best treatment is at each disease stage.”

Incorporating FLT3 tyrosine kinase inhibitors into the treatment of patients with FLT3-mutant AML has become standard of care, Dr. Wang noted. We have moved from first-generation FLT inhibitors such as lestaurtinib, midostaurin, and sorafenib to second-generation agents such as quizartinib, crenolanib, and gilteritinib. Studies have shown that targeted therapies (eg, quizartinib and gilteritinib) seem to yield better outcomes than chemotherapy alone in treating resistant FLT3-mutant AML.

As for other inhibitors, ivosidenib (IDH1 inhibitor) and enasidenib (IDH2 inhibitor) are being used in the newly diagnosed or relapsed setting, respectively, for IDH-mutant AML. Although neither of these drugs is curative, noted Dr. Wang, they offer many patients a clinical benefit. In addition, the BCL-2 inhibitor venetoclax, along with low-dose chemotherapy, has become the standard of care for older patients with AML.

Finally, although immune checkpoint inhibitors have been somewhat disappointing in the management of AML, Dr. Wang briefly mentioned a potentially more promising approach: targeting specific antigens expressed on leukemic cells with novel antibodies. For instance, the monoclonal antibody magrolimab, which targets CD47, has been studied in combination with azacitidine, with some success.

Disclosure: Dr. Wang has received consulting fees from AbbVie, Astellas, Daiichi Sankyo, Jazz Pharmaceuticals, Kite Pharma, Celyad, Stemline, and Pfizer and has received honoraria from Stemline and Pfizer.


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