Barriers to Molecular Testing in AML
Eunice S. Wang, MD, offers an overview of common barriers to performing molecular testing in community practices, including uncertainty about which tests to perform and the wait times for results.
Transcript:
Naval G. Daver, MD: What are the barriers in the community setting to getting these molecular tests?
Eunice S. Wang, MD: In our community, I think a lot of the practitioners are busy. They’re seeing lots of patients with lots of different diagnoses. And I think it’s difficult for them to remember what to order and what to follow necessarily on patients. One barrier is, as mentioned by Dr Pollyea, that it can take a couple of weeks for molecular and genetic results to come back. And patients are anxious, clinicians are anxious, and they don’t know whether it’s safe to wait for that. I think also there’s confusion about what type of molecular tests to [order]. At our center, we have a next-generation myeloid panel that can result in 3 to 5 days even with the panoply of these mutations. Cytogenetics take about the same amount of time or even less. And there’s PCR; I think that we do targeted PCR for things like FLT3-ITD. And, again, quantitative PCR for molecular MRD is increasingly being ordered for NPM1 mutatations to follow disease at the time of remission. And we’re starting to see FLT3 next-gen[eration] sequencing being used for MRD purposes as in the MORPHO trial. So, I think it’s important to have the collaboration and, as was mentioned, the knowledge that you need to do targeted … PCR testing for FLT3 and NPM1, next-gen[eration] sequencing for some of the other ones. Cytogenetics, you must remember that KMT2A is a cytogenetic rearrangement. It’s not a mutation, so you must wait for conventional cytogenetics or fluorescence in situ hybridization (FISH) results to identify those. But the importance of looking at these at the time of diagnosis is that may be the only time that you have significant disease burden to establish your baseline. If you don’t look for them at diagnosis, you don’t get NPM1-mutant PCR. You don’t get your cytogenetics. Then you don’t select the targeted therapies, and if you do select the targeted therapies you don’t know how necessarily to monitor them, which harkens back into again monitoring the disease at the time of remission, monitoring it prior to transplant, because those are significant prognostic indicators of outcome in these patients.
Harry P. Erba, MD, PhD: Naval, if I can add to that.
Naval G. Daver, MD:Yes, please.
Harry P. Erba, MD, PhD: I agree with everything that Dr Wang just said … There are truly practical issues, though. Think about the patient who gets sent to the emergency [department] with pancytopenia and they have pneumonia or they need transfusions, and they see some blasts. And the next thing you know they’re put in the hospital. So, they’re in the hospital and there is a need to make a diagnosis and start treatment quickly, or an apparent need. And what I’d like to remind [individuals] of is that that patient did not come to the hospital thinking they’re going to be there for a month, getting initial therapy for AML. And they may not need that, especially in the patients who present with leukopenia or pancytopenia, [and] don’t have proliferative disease. You may be able to do your bone marrow biopsy, get all the testing done that Eunice went through so well, that whole panel, and send the patient home after you’ve treated their febrile neutropenia on oral antibiotics or given them a red cell transfusion. It’s a little bit different when the patient presents with leukocytosis where you really need to get the disease under control, and they may be sick and need an immediate treatment of leukostasis with cytoreductive therapy like hydroxyurea or a single dose of cytarabine, as I know you do in your institution. But for most of our patients, especially older, I think we need to think outside the box and think that they’re not really stuck there. They got admitted for a reason. You can treat that reason, discharge them, have them follow up in clinic, and in most cases the patients will be very appreciative of that because they must come to grips with this life-altering diagnosis that they’ve been left with. So that is something I try to stress. I would say the biggest barrier to getting this done, the blame falls on us because the leukemia experts [who] have come before us said you need to start treatment right away. And that’s something we need to dispel, not universally, but in selected situations.
Naval G. Daver, MD: I think that’s important, that it is now the recommendation, pretty much all of us in [the United States] and Europe to wait for key molecular testing results, of course taking into account specific scenarios, right? If you have an FLT3 with 100,000 white [blood cell] count, of course you cannot wait, but you could cool that patient off. You could do cytarabine. Some people do Hydrea [hydroxyurea]. Some [individuals] do etoposide. Whatever you’re comfortable, have done in the past, get the white count down, monitor the patient closely. If they’re stable, they can go outpatient for a week, come back with labs done every other day or so. If they’re not, we watch them inpatient. But yes, absolutely to Harry’s point, we are changing our recommendation completely on its head from 20 years ago [when] we said the sun should not set on leukemia. Now we’re like, please don’t start treatment right away without getting key molecular [testing] with close monitoring. But I think that’s just because we have things that work and improve not only response, but survival, posttransplant outcome. And so, this is something we’re seeing across many tumors, solid tumors, others where molecular testing is becoming quite critical.
Transcript is edited for clarity and readability.
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