Michael J. Mauro, MD, the leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses the risks of disease progression in myelofibrosis.

Although disease progression presents differently across the spectrum of myelofibrosis, the threat of transformation to acute myeloid leukemia (AML) remains a significant challenge, Mauro says. The treatment plan of patients who progress to accelerated or blast phase myelofibrosis often needs to be altered in anticipation of AML transformation; however, some approaches will continue patients on their current therapy, such as ruxolitinib (Jakafi), to prevent anti-inflammatory escape or continue clinical benefit, Mauro explains. Often, surveillance for progression in myelofibrosis can identify features of leukemic transformation, such as new mutations in driver genes and sudden changes in allelic fractions. 

Additionally, patients with progressive myelofibrosis may experience more profound cytopenias that can indicate more aggressive disease or poor disease control, Mauro says. Other signs of disease progression include splenomegaly, thrombosis, inflammation, generalized organ dysfunction, weight loss, and hypoalbuminemia, Mauro concludes. 

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Michael J. Mauro, MD, discusses the risks of disease progression in myelofibrosis.  



Dr. Mauro on the Risks of Disease Progression in Myelofibrosis 

Michael J. Mauro, MD, the leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses considerations for early treatment initiation in myelofibrosis.

Disease progression occurs on a spectrum in myelofibrosis, ranging from asymptomatic disease to radiographic disease progression or pathologic disease progression, Mauro explains. However, progression is most often driven by symptom burden, Mauro adds. 

Ruxolitinib (Jakafi), the mainstay of treatment in myelofibrosis, is associated with symptom management and quality of life (QOL) improvement, Mauro says. However, patients without significant symptom burden, which would be indicative of treatment initiation, could still be treated early, Mauro explains. Early utilization of chronic maintenance treatment can reduce splenomegaly and improve blood counts, as well as potentially alter the natural biology of the disease, Mauro says. As such, patients who have some critical mass of symptoms in which treatment is warranted should be treated early, Mauro concludes. 

Michael J. Mauro, MD, discusses considerations for early treatment initiation in myelofibrosis.  



Dr. Mauro on Considerations for Early Treatment Initiation in Myelofibrosis 

Michael J. Mauro, MD, a hematologist and leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses updates in chronic myeloid leukemia (CML).

There are now 4 agents approved in the frontline setting for chronic phase CML. Mauro says that novel treatments in the frontline setting for CML were a big topic during the 2017 ASH Annual Meeting, and the FDA approval of bosutinib (Bosulif) as a first-line treatment for patients with Philadelphia chromosome-positive (Ph+) solidified that.

Mauro says that another important topic in CML is how to conceptualize treatment-free remission. This is exciting, Mauro adds, because tyrosine kinase inhibitors (TKIs) have allowed patients to experience substantial remissions.

Additionally, cardio-oncology is an important consideration for physicians treating patients with CML, Mauro says, as well as investigating fourth-generation drugs.

Michael J. Mauro, MD, a hematologist and leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses updates in chronic myeloid leukemia.
 

Dr. Mauro Discusses Updates in CML

Michael J. Mauro, MD, a hematologist and leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discusses some of the emerging and current therapies for patients with myeloproliferative neoplasms (MPNs).

There have been some large questions in the field of polycythemia vera (PV) and thrombocytosis for essential thrombocytopenia (ET). Additionally, he adds, an ongoing trial of high-risk patients is asking the question of whether frontline interferon versus hydroxyurea is more effective. At the 2016 ASH Annual Meeting, a study presented demonstrated fairly equal results regarding hematologic response, bone marrow, and molecular response. However, longer follow-up is needed, he says.

Regarding the use of ruxolitinib (Jakafi) in myelofibrosis, Mauro also questions if there is a different JAK inhibitor that could offset some of the anemia observed with ruxolitinib. There are updated data from studies of pacritinib, another JAK inhibitor, with the possibility to be useful in patients with low platelets, he explains.

There has also been updated findings with the JAK inhibitor momelotinib that could possibly offset anemia. Some trials showed that it offered some similar benefits of ruxolitinib, but not as complete as anticipated.   

Dr. Mauro on Current and Emerging Agents for MPNs

Michael J. Mauro, MD, hematologist, leader of the Myeloproliferative Neoplasms Program, Leukemia Service at Memorial Sloan Kettering Cancer Center, discusses how to best select therapies for patients with chronic myeloid leukemia (CML).

With five oral tyrosine kinase inhibitors and three agents available for patients in the frontline setting, Mauro says the challenge with selecting therapies is a good problem for oncologists to have. He advises them to have an understanding of side effects associated with each agent, as well as to take an individualized approach with patients. Promising therapies include nilotinib, dasatinib, and imatinib.

The next step after selecting an upfront therapy involves evaluating early responses in case switching treatments is necessary. In second-, third-, and fourth-line settings, treatment options remain broad. Disease stage, prior exposure, and genetic mutations are all factors that can be used to select therapies in these settings.

In the next few years, Mauro predicts researchers will have more data on side effects, cardiovascular risk, and using aggressive therapy as an upfront approach.

Michael J. Mauro, MD, hematologist, leader of the Myeloproliferative Neoplasms Program, Leukemia Service at Memorial Sloan Kettering Cancer Center, discusses how to best select therapies for patients with chronic myeloid leukemia. 


Michael J. Mauro, MD

Articles

Dr. Mauro on the Risks of Disease Progression in Myelofibrosis

Dr. Mauro on Considerations for Early Treatment Initiation in Myelofibrosis

Dr. Mauro Discusses Updates in CML

Dr. Mauro on Current and Emerging Agents for MPNs

Dr. Mauro on Selecting Therapies for Patients With CML