Boom in Targeted Agents Propels AML Treatment Into a New Era of Personalized Care

Christina T. Loguidice
Published: Tuesday, Jun 12, 2018
 Harry Erba, MD, PhD

Harry Erba, MD, PhD
An estimated 19,520 new cases of acute myeloid leukemia (AML) are expected in the United States in 2018, representing approximately 1.1% of all new US cancer cases.1 Until 2017, there was little drug development in AML—treatment largely revolved around standard chemotherapy regimens, as it had for the past 40 years. By the end of 2017, however, there were 4 new drug approvals by the FDA , as well as many other agents showing promise in clinical trials (Table2-9). These treatment advances have been attributed to increased understanding of molecular drivers of AML. During an OncLive Peer Exchange® moderated by Harry Erba, MD, PhD, a panel of AML experts discussed these newly approved agents and provided insight on how they are rapidly changing the standard of care for various AML subgroups. They also provided insight on several promising agents on the horizon.

Newly Approved Agents

All 4 newly approved AML drugs are targeted agents, but each targets the disease in different ways. “CPX-351 [Vyxeos] is the liposomal daunorubicin/cytarabine formulation that’s targeted to a clinically defined group of patients: those with treatment-related AML and AML with myelodysplasia-related changes. Then there are 2 drugs targeted to mutations: midostaurin [Rydapt], for patients with previously untreated AML with FLT3-ITD or FLT3-TKD mutations, and enasidenib [Idhifa], which is the oral IDH2 inhibitor approved for IDH2-mutated AML in relapsed or refractory disease. Finally, we have a different kind of targeted therapy, an antibody–drug conjugate against CD33: gemtuzumab ozogamicin [Mylotarg],” Erba said.

at the time of diagnosis because the next-generation sequencing panel may miss it,” Erba said.

Table. Newly Approved and Investigational Targeted Agents in AML2-9

Second, the panelists warned about midostaurin toxicities and drug interactions. “One of the issues we’ve had practically is that it can cause QTc prolongation. It interacts with azoles. Part of that may be because it’s such a broad spectrum in pan-kinase inhibition,” Wang said. Dose reduction is rarely necessary, she noted, and interval assessments of QT by electrocardiogram are often sufficient in patients taking midostaurin concurrently with medications that can prolong the QT interval.
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Advances in™ Multiple Myeloma: Changing Treatment Paradigms and the Emerging Potential of CAR T-Cell TherapyAug 30, 20191.5
2nd Annual Live Medical Crossfire®: Hematologic Malignancies OnlineSep 28, 20198.0
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