Balancing the desire for quick AML results with precision genetic testing

When a patient is diagnosed with AML, it is rightly considered a medical emergency because they can deteriorate rapidly. As any oncologist or pathologist knows, the risk of infection, bleeding, and anemia are elevated, so immediate attention is justified.

Where the line has been less clear is when to initiate treatment of AML: immediately upon diagnosis using traditional methods such as bone marrow biopsy or spinal tap, or after genomic test results come back, which often provide subclassification of AML that indicates more personalized treatment? It may appear that the urgency to initiate treatment trumps waiting for seven or even ten days for genomic test results. Yet as is often the case in these debates, the reality is subtler and more nuanced. 

Several recent articles and studies have challenged the notion that it is necessary to start AML treatment immediately. Other studies that have looked at outcomes within the first 7 days versus the next 7 have not shown a significant difference in terms of outcome overall.¹

In addition, there is new data that speaks to the value of having a comprehensive genomic assessment to tailor appropriate therapy for the patient.² This is to be expected as diagnostics have evolved to keep up with our growing understanding of the disease over the past 50 years.

For example, it has become clear that specific alterations in certain genes could fundamentally influence the development of certain forms of leukemia. More recently, it also has become evident that certain activated genetic mutations could be the targets for specific therapies. The addition of FLT3 inhibitors to FLT3-ITD positive leukemias does improve outcome in those patients. Similarly, those patients with IDH2 or IDH2 mutations have improved outcomes when treated with IDH2 inhibitors.³

In essence, our field has been incorporating both individual gene and genomic alterations into an ever-broader classification scheme. This wider genetic aperture is important for both risk assessment and treatment strategies which may influence a course of action such as a bone marrow transplant. 

Test turnaround times have continued to drop in AML testing. Flow cytometry tests now take 24-48 hours. Individual molecular testing can be turned around similarly quickly. Larger next-generation sequencing (NGS) panels typically average 10 days, but can extend to 14 days depending on test repeats and other factors. This may seem like a long time when considered in isolation, but what is becoming more common is an oncologist diagnosing a patient using traditional tests, then ordering more comprehensive panels if the diagnosis comes back positive. Others will order specific individual tests like IDH1 and IDH2, then order a genomic test because they want that information to determine precise treatment strategies. They simply don’t need it to make the initial assessment.

Other factors that need to be weighed in determining testing protocols include:

• Comorbidities. Certain patients have a comorbidity that requires treatment before being able to sustain AML chemotherapy
• APL. With Acute Promyelocytic Leukemia (APL), patients have a high risk of going into disseminated intravascular regulation (DIC), which can be a life-threatening process in and of itself. With APL, it’s important to conduct confirmatory molecular testing such as FISH or karyotyping as soon as possible to support the use of retinoic acid and arsenic to treat the patients. This is very different than standard deduction chemotherapy
• Patient preference and empowerment. Patients may ask for time to get personal affairs in order before undergoing chemotherapy. And as empowerment of patients in their own care becomes a natural part of the oncology treatment process, they may ask to initiate treatment sooner or later for any number of reasons

Pathologists and oncologists need look no further than the NCCN guidelines to confirm that the industry has recognized that legitimate reasons for delay exist, and that having comprehensive genomic information on patients at hand may help guide therapy.⁴

As an oncologist or pathologist, it’s important to look at several criteria when assessing AML testing providers. These include but are not limited to these 7:

1. The ability to act as a full-service hematopathology provider, not just a test provider
2. Geographic reach of the provider’s labs, especially when fast turnaround is essential
3. Depth of experienced hematopathologists on staff who diagnose leukemias on a daily basis
4. Responsible testing practices that help the clinician balance the best information with the most informed treatment decision
5. A comprehensive portfolio of tests as well as availability of clinical care pathways that encourage guideline-recommended testing to be performed more rapidly  
6. Result notification policy that ensures clinicians are notified of test results regardless of day or time
7. A proven ability to work with payers to show that their tests meet guidelines and have the clinical utility that would merit coverage

The good news amidst the recent, demographic-driven rise of AML,⁵ at least in the US, is that the number of testing options has never been greater. As long as you work with a diagnostic provider you can trust, the ability to offer more targeted treatments at the right time can only be a precursor to more hopeful outcomes for everyone. It’s all about giving the oncologist the most relevant information to determine the best treatment strategy.