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Landscape for Myeloproliferative Disorders Becoming More Defined With Improved Treatments, Biomarkers

Elizabeth Leick and Gina Columbus
Published: Wednesday, Jan 11, 2017

Michael J. Mauro, MD

Michael J. Mauro, MD

Emerging therapies in myeloproliferative disorders such as chronic myeloid leukemia (CML), polycythemia vera (PV), and myelofibrosis could have the potential to shake up the landscape. But, during the 2016 OncLive® State of the Science Summit on Hematologic Malignancies, Michael J. Mauro, MD, noted that there is a great deal of work ahead for researchers.

“It's still a battle for patients,” said Mauro. “They still have long journeys, side effect management, a lot of decision making with multiple medications, and new drugs on the horizon. However, this is a very good ending to what was really the breaking story of targeted therapy in cancer.”

In an interview during the meeting, Mauro, a hematologist and leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses the major questions regarding the current state of CML, as well as explorative options for patients with PV and myelofibrosis.

OncLive: What did you lecture on at this State of the Science Summit?

Mauro: Regarding state of the art for CML, some of the major questions we have are, “What is new from a therapeutic standpoint for patients with highly resistant CML?” and “Can patients who have been on therapy and are in deep remission stop therapy?” There were a number of presentations at the 2016 ASH Annual Meeting about these topics.

There was a presentation of updated data from the phase I trial of ABL001—which is a fourth-generation tyrosine kinase inhibitor (TKI) that is given orally once or twice daily—showing very good safety and preliminary efficacy for patients with any stage of CML. We have a phase II dose established and a real signal that this drug could not only be a drug used in the salvaged setting, but perhaps combined earlier in lines of therapy.

Also, at the 2016 ASH Annual Meeting and in the last year, we have seen a lot of development around treatment-free remission. There's been a change in the NCCN guidelines that were just updated for CML. We now have a little rulebook to go by through the NCCN. That wasn't really the case before, it was really just regulated through clinical trials. We have more mature data coming out of ASH for patients from a larger European trial. It's a little bit better guidance on how long a patient should be in treatment, how long they should be in deep remission, and more.

Some other studies from ASH showed us that maybe patients can reduce their dose of a TKI before a discontinuation without showing significant relapse. There was also a little more information on the type of factors that play into what patients are successful with treatment-free remission. This includes changes in the immune system, the immune cell repertoire, and patients who are successful with TKI therapy. Those are the highlights for CML.

What are some of these pivotal studies for CML?

The EURO-SKI trial looked at the success of treatment-free remission in a very large number of patients—over 700—from Europe. Part of the most innovative findings was learning patients need to be on TKI or in deep remission for about 5.8 years for it to be the most successful. That was the dividing line where success was higher versus lower.

We are starting to shape the picture of what a patient with CML might need to look like before they can think about treatment-free remission, from the EURO-SKI trial.

What do you imagine the landscape of CML looking like in 5 to 10 years?

For myeloproliferative disorders—CML specifically—we're getting better and better targeted therapies. We're really coming “full circle” in that we're not only putting a high fraction of patients in remission without what people consider conventional chemotherapy, but we are really talking about a functional cure, which plenty of people didn't think was possible. That is great news.

What are the optimal ways of managing some of these side effects?

Decision making for patients with CML takes some thought and finesse. First, TKI therapy is based on patients' profiles and perhaps their comorbidities. Comorbidities play an important role in CML. They may have more of an impact than CML responses shown in a recent paper by Germans in the Journal of Clinical Oncology. The side effect management encompasses knowing what a patient's comorbidities are and thinking TKI may be best for them. When you're looking at resistant disease, you're obviously going to think a little bit differently about comorbidities. However, they need to be managed.

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