Genomic Testing Should Be Standard in Myelofibrosis at Diagnosis, Says Rampal


Raajit K. Rampal, MD, PhD, discussed the role of genomics in the treatment landscape of myelofibrosis and the remaining challenges that need to be addressed in order to use this information more effectively to treat patients and improve outcomes.

Raajit K. Rampal, MD, PhD

Raajit K. Rampal, MD, PhD

Patients with the myeloproliferative neoplasm (MPN) myelofibrosis should be tested upfront for potential genomic targets that could help in the treatment decision process, according to Raajit K. Rampal, MD, PhD. For example, the JAK/STAT pathway can be targeted with a JAK inhibitor, such as the FDA-approved JAK inhibitors ruxolitinib (Jakafi) and fedratinib (Inrebic).

By identifying potential therapeutic targets, these targeted therapies could be used more efficiently in patients with myelofibrosis, or they could also serve as predictors of response to standard regimens. Patients with myelofibrosis already are associated with a poorer life span than those diagnosed with other MPNs, which underscores the importance of improving patient outcomes in this setting.

During the 2020 Society of Hematologic Oncology (SOHO) Annual Meeting, Rampal reviewed the current role of genomics in myelofibrosis during his presentation. He also highlighted how this can be used in clinical practice. Rampal believes that all practices should incorporate genomic testing earlier on in the treatment of patients with myelofibrosis, specifically at the time of diagnosis.

In an interview with Targeted Oncology, Rampal, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discussed the role of genomics in the treatment landscape of myelofibrosis and the remaining challenges that need to be addressed in order to use this information more effectively to treat patients and improve outcomes.

TARGETED ONCOLOGY: Could you provide an overview to your presentation?

Rampal: The focus of the presentation was to discuss how we can leverage genomics to deliver care in the modern era for patients with myelofibrosis. There has been an explosion in our understanding since 2015 of how the genomics contribute biologically but also what they mean clinically to patient care, so we're at a point where the genomics can help us to inform treatment decisions.

TARGETED ONCOLOGY: How do genomics inform treatment decisions in myelofibrosis?

Rampal: First and foremost, they give us prognostic information. We've known for some time, for example, that CALR mutations in patients seem to have a lower risk of progression, relatively speaking, versus JAK2-mutant patients, but also that there are a number of high-risk mutations, high risk, meaning that there is an increased risk of disease progression. It becomes complex when trying to put all of these things together, but fortunately, we now have several tools that are clinically used that incorporate all of these genomic findings with clinical findings. Clinical characteristics that we've known for some time have prognostic significance, and so we now have readily accessible tools that we can use in the clinic to take a patient's information clinically, as well as genetically, to come up with a risk score for disease progression.

TARGETED ONCOLOGY: What are these different therapeutic approaches being used?

Rampal: The major point is that the risk stratification tools right now don't tell us how to treat the patient. What they do tell us is what the risk of progression is, so whether there is an implication with regards to treatment. The answer is potentially yes. If a patient has a relatively high risk of progression, in the short-term, it may be reasonable to try to refer that patient for an allogeneic stem cell transplant, whereas if somebody has a very low risk disease, then transplant is probably not something we need to entertain at that given point. Does it tell us though, when to use a JAK inhibitor or other therapies? It does not do that at this point.

TARGETED ONCOLOGY: What are the biggest challenges with using genomics right now in this space?

Rampal: I think first is standardization. Increasingly, people are using large genomic panels that have most of the genes of interest, but is this universal? No. I think oftentimes that people start the workup by testing for a JAK/STAT driver mutation, and then sometimes, but not always, people will get the larger genomic profiles. I think 1 of the most important things is making sure everybody knows that in 2020, this should be considered standard of care to get the broad genomic panel.

The second thing is how to use it, and that was part of the discussion at the meeting. It's not always immediately obvious, but the scoring tools that we have tend to be very user-friendly. I think that increasingly, we will hopefully see people starting to use them, and then make decisions from there.

TARGETED ONCOLOGY: What are your key takeaways from this presentation?

Rampal: It's important to recognize that mutations outside of the JAK/STAT pathway have an important prognostic role in the treatment of MPN patients. It can tell us the patient's risk of progression, but it can also tell us whether or not a patient is likely to have a sustained response to treatments like ruxolitinib. That can also help clinicians make decisions.

In 2020, I think it is absolutely standard of care to get the mutation profiling done at the time of diagnosis, but it's also important to recognize that mutations can evolve over time. It is reasonable to think about repeating genomic testing during the course of a patient's disease because the genomics can certainly change and, as a result, so can implications for the patient's long-term prognosis.

TARGETED ONCOLOGY: What is the prognosis typically like for patients with myelofibrosis compared with the other MPNs?

Rampal: Generally speaking, the life span is shorter than in patients with polycythemia vera or essential thrombocytosis. There's also a higher risk of progression to acute leukemia.

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