Clinical pathways are prone to criticisms that they do not take patient diversity or the latest clinical advances into account, both of which can be addressed through comprehensive pathway design and updating strategies. These challenges are illustrated by clinical pathways for acute myeloid leukemia (AML), the management of which is complicated by the diversity of patient characteristics—including age, comorbidities, and genetic mutations—that influence prognosis and generate discrete therapeutic recommendations for individualized care.
How do recent therapy advances and heterogeneous patient characteristics contribute to overall complications in developing and updating pathways in AML?
I think one of the challenges in our field is the rapid development of targeted therapies and the deluge of opportunities we have to expand our paradigm for managing our patients. It will take time for us to better understand how to incorporate [these therapies] into guidelines, pathways, and recommendations. There are certain scenarios, for example, where patients may have multiple, targetable opportunities in terms of treatment. For example, an AML patient may have an FLT3 mutation and an IDH mutation in the relapse setting—in time, we may have drugs available to target both mutations in that setting, and, as physicians, we have to better understand how best to sequence those therapies. Additionally, there are other components to think about such as the cost of treatment—these drugs are expensive. Getting payers to agree to pay for them may be a challenge over time, depending on where you are in the country, what setting you have, what insurance the patient may have, or the hospital where they are being cared for.
What are some of the novel therapies that you anticipate being the most practice-changing?
I think all of them are practice-changing, because all of them, in some ways, have been incorporated into therapeutic guidelines/recommendations. I can tell you that, in our practice, patients with IDH mutations who have advanced relapsed/refractory disease, we do try and [prescribe] ivosidenib if they have an IDH1 mutation, or enasidenib if they have an IDH2 mutation. For patients who have FLT3 mutations, are newly diagnosed, and are appropriate for intensive induction treatment, we add midostaurin to induction, because the survival advantage was demonstrated in the phase 3 RATIFY study.
In general, the practice is evolving. The FDA approvals have led to the incorporation of new drugs, and we will have to see, as more drugs are approved, how we are going to potentially bring them in: how are we going to combine, how are we going to sequence, how we are going to further develop our paradigms and recommendations.
How has your hospital remained at the forefront of AML research and treatment?
It takes a lot of effort and coordination—running a clinical trials program has many factors to consider. You have a team of clinical research coordinators, clinical research associates, research nurses, and investigators; you have the protocol office that sort of manages the intake of trials; you have institutional review board meetings and scientific review committee meetings. A lot of infrastructure needs to be in place to look at promising protocols, implement them, and render them available for patients.
As the director of the leukemia program, and also the person that helps guide the clinical research there over the last several years, it has been important for me to make available to patients in our area the newest, most promising drugs that are available in clinical trials, because we are far from curing AML. AML still is a largely lethal disease; still a minority of patients are cured, so it is very important to have a robust clinical trials structure, because without it you are not going to advance the field, and you are not going to make the progress that needs to be made.
The progress that we have seen today was only possible through doing these clinical trials. So my goal is to have a well-oiled machine with very good people that run the clinical trials, an infrastructure in place, and also mindfulness of what is promising out there that is going to help potentially change the standard of care and practice.
This educational activity was supported by an educational grant from Daiichi Sankyo, Inc, and Jazz Pharmaceuticals, Inc.