Alexander E. Perl, MD, MS, associate professor, medicine, the Hospital of the University of Pennsylvania, discusses why genetic testing is important for determining targeted therapies for patients with acute myeloid leukemia (AML).

Newer targeted therapies in the AML treatment landscape are providing impressive benefits for patients. For instance, although single-agent gemtuzumab ozogamicin (Mylotarg) did not display a prominent overall survival (OS) improvement in the relapsed/refractory setting, when moved to the frontline setting and combined with induction and consolidation chemotherapy, the agent demonstrated an impressive OS benefit in patients with core binding factor AML, Perl says.

Similar advances have been made in patients with 

-mutated AML. The phase 3 RATIFY trial (NCT00651261) led to the FDA approval of midostaurin (Rydapt) in 

-mutant AML based on the survival improvements it showed with the agent in the ITD and TKD subtypes of 

-positive disease, Perl explains. Additionally, the phase 3 QuANTUM-First study (NCT02668653) showed OS improvements with quizartinib, a FLT3 TKI, in older patients with the ITD subtype of 

-mutant AML, Perl notes. Determining patients’ genetic risk profiles is important for recognizing potential therapeutic targets, so patients can receive optimal therapies early in their treatment courses, Perl concludes.

Videos

Alexander E. Perl, MD, MS, associate professor, medicine, the Hospital of the University of Pennsylvania, discusses why genetic testing is important for determining targeted therapies for patients with acute myeloid leukemia.

Dr. Perl on Genetic Testing and Targeted Therapies in AML

Alexander E. Perl, MD, MS, associate professor of medicine, Perelman School of Medicine, University of Pennsylvania, discusses the challenges of using immunotherapy with antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and CAR T-cell therapies in acute myeloid leukemia (AML). 

Currently, the main ADC that is being used in clinical practice is gemtuzumab ozogamicin (Mylotarg), which is approved for the treatment of adult patients with newly diagnosed CD33-positive AML, says Perl. However, other potential agents are in early development and are being used exclusively in clinical trials, adds Perl. 

Specifically, bispecific antibodies are showing promise in this space; however, questions regarding optimal targets, payload, and drug delivery still need to be answered. 

CAR T-cell therapy has shown success in acute lymphoblastic leukemia (ALL), but are much harder to create in AML. The myeloid blasts, the tumor cells in AML, are shared with normally-occurring hematopoietic elements in healthy cells, Perl explains. An agent that effectively kills those cells may result in increased extramedullary or marrow toxicity against normal cells that you might wish to preserve, concludes Perl.

Alexander E. Perl, MD, MS, discusses the challenges of using immunotherapy with antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapies in acute myeloid leukemia. 
 

Dr. Perl on Challenges of Implementing Immunotherapy in AML

Alexander E. Perl, MD, MS, associate professor of medicine, University of Pennsylvania, Perelman School of Medicine, discusses how to assess what therapy is best for patients with acute myeloid leukemia (AML). 

In the past, AML treatment was largely a one-size-fits-all approach. Patient fitness was the only criteria that was used to determine whether to administer induction 7+3 chemotherapy, low-intensity treatment with low-dose cytarabine or hypomethylating agent, or supportive care for patients who could not tolerate either therapy. 

Today, the genetic composition of the leukemia is used to determine the optimal therapy. Fitness still plays a role in determining whether a patient should receive intensive or low-intensity treatment. Notably, induction strategies that are personalized to the genetic makeup of the disease result in improved survival, says Perl. 

Personalized approaches confer improved survival across subtypes of AML, adds Perl, including therapy-related AML, myelodysplastic syndrome-related AML, 

-mutant AML, and core-binding factor AML. 

Alexander E. Perl, MD, MS, discusses how to assess what therapy is best for patients with acute myeloid leukemia. 
 

Alexander E. Perl, MD, MS

Articles

Dr. Perl on Genetic Testing and Targeted Therapies in AML

Dr. Perl on Challenges of Implementing Immunotherapy in AML

Dr. Perl on Choosing the Optimal Therapy in AML