How Genomic Testing and Targeted Therapies Are Shifting the Mindset for Treating Acute Myeloid Leukemia

September 18, 2020
Sponsored by Astellas

Questions and answers with Dr. Eunice Wang, Chief of Leukemia at Roswell Park Comprehensive Cancer Center, an unpaid Astellas consultant

Q: How did you become interested in treating patients with Acute Myeloid Leukemia (AML)?

When I was a freshman at Harvard University, my classmate and study group partner was diagnosed with acute leukemia. After undergoing treatment, he passed away the following summer. That experience had a profound impact on the trajectory of my career. That same summer I went to the Dana Farber Cancer Institute in Boston, MA, and I volunteered to work in a laboratory performing leukemia research. In the years that followed, I developed strong relationships with my physician-scientist mentors, who encouraged me to pursue medical school with a specialty in hematology/oncology—specifically hematological malignancies.

When I first started practicing as an oncologist, I realized that most elderly AML patients struggled to tolerate the high dose chemotherapy that was the only option for treatment at the time—and, for lack of better options, were placed into palliative hospice care. I felt these wonderful individuals, who had lived robust lives, deserved more. That really was the motivation for me.

Particularly in the last few years, I’m glad I made the choice to focus on acute leukemia, as we’ve seen an explosion of new therapies for AML. The field is transforming, and we are no longer approaching the disease the same way we did 20 years ago. It’s a really exciting time to be working with and treating AML patients.

Q: Why is mutation testing critical for AML patients, including those with relapsed or refractory disease?

AML is a very diverse disease, with multiple mutations at diagnosis that also change over the course of treatment. To provide hope and prolong survival for people with AML, it’s critical to understand the underlying biology of the cancer. With this information at our fingertips, we can make informed choices about more effective and less toxic treatments. For example, I would argue that no oncologist is treating breast cancer without first receiving genetic results. Genomic testing for AML patients should be no less important.

In fact, foregoing genomic analysis or not waiting for the results could lead to worse outcomes for patients. And, in a disease with poor survival, getting individuals into remission is critical.

I run a small translational leukemia lab and have also been involved in numerous clinical trials for patients with AML characterized by mutations in the FLT3 gene. In patients with relapsed or refractory AML, targeting this abnormal gene mutation with an oral inhibitor has been shown to be more effective in inducing remissions and prolonging survival than intravenous chemotherapy. This represents a significant shift in the mindset for a physician—to be able to treat actionable mutations in acute myeloid leukemia with oral medications—but that’s what we have been able to do for certain patients.

Q: At what stage in a patient’s disease should HCPs and patients plan for mutation testing?

Mutation testing should be performed at diagnosis of AML and at every sign of disease recurrence in an individual patient. Because of the aggressive and diverse nature of AML, genetic events can evolve over the course of a patient’s treatment journey, making testing at the time of relapse absolutely essential. The biological disease of AML could be completely different at relapse or refractory disease versus at diagnosis.

In relapsed and refractory—as well as newly diagnosed—AML, you need to determine if a FLT3 or other genetic mutation is present in order to choose optimal treatments.

Q: Recognizing that each patient may respond differently to treatment, can you share some examples of cases where mutation testing has changed the course of treatment and/or disease progression for your patients?

A: I recently treated a lovely 67-year-old woman whose disease presented with high white blood cell and low platelet counts. After two rounds of chemotherapy and an experimental trial with no response—her AML was highly resistant—we repeated her genomic testing and found evidence of a new FLT3 mutation.

After the patient was started on a targeted FLT3 inhibitor, her blast counts dropped significantly. A bone marrow biopsy showed disease control, and she was able to proceed onto an allogeneic bone marrow transplant from her brother. She is still alive today, several months later.

Q: How has COVID-19 affected your AML patients and practice, including both diagnosis and treatment?

A: Because AML is a clinically aggressive disease, I have continued to treat my AML patients throughout the pandemic. Our ability to diagnose new patients and treat existing patients has not changed, including genomic and cytogenetic testing. However, because patients with blood cancers may be at higher risk of contracting the virus and are potentially more likely to suffer severe consequences from infection, delivery of patient care has changed in order to minimize potential exposure of patients. We have incorporated more virtual office visits in place of on site visits and have coordinated therapy closer to home for those patients who live at a distance from our facility.

Different approaches for chemotherapy in individuals newly diagnosed with blood cancer who also have active COVID-19 infection have been developed. Recently I saw a young patient with newly diagnosed acute leukemia who I chose to treat initially with a less suppressive, lower-dose chemotherapy regimen so as to not further compromise his immune system’s ability to fight the virus. Unfortunately, because many patients in this situation may not be able to optimally fight off the virus in the setting of active cancer, the decision of when to start therapy is a challenging one. As the pandemic appears to be here to stay for some time, I am looking forward to our center’s and community’s ability to continue testing of our cancer patients to ensure the safety of our patients and staff in the coming weeks.

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