Treating patients with MPN and related disorders according to underlying risks

02 Jul 2021

When managing patients with myeloproliferative neoplasm (MPN), Dr. Gill, Harinder Singh Harry described age, cardiovascular risk factors and a history of thrombosis as the major risk factors for thrombosis in polycythemia vera (PV). On the other hand, JAK2V617F mutation is an additional risk factor associated with essential thrombocythemia (ET).

In patients with low-risk PV, phlebotomy is typically performed to maintain a hematocrit of <45%. Low-dose aspirin coupled with monitoring of new thrombosis or bleeding as well as the signs and symptoms of disease progression should also be given to manage the potential cardiovascular risks. In addition, cytoreduction should be considered for patients with high white blood cell (WBC) count, new thrombosis or disease-related bleeding, or frequent and persistent need for phlebotomy but with poor tolerance to phlebotomy.

In patients with high-risk PV, low-dose aspirin and cytoreduction should be given. When performing cytoreduction, Dr. Gill noted that ruxolitinib can be considered for patients with HU resistance and intolerance. Otherwise, hydroxyurea (HU) and pegylated interferon alpha (PEG-INFα 2A/2B) can be given if not previously used, and the recently available ropeginterferon alfa- 2B is also an efficacious option with a high overall response rate of 90%.1 That said, Dr. Gill noted that HU is not recommended for young patients or pregnant women and an alternative should be considered for these patient groups.

In patients with very-low to low-risk ET, aspirin should be given regardless of underlying risk factors unless acquired von Willebrand disease (vWD) or other platelet dysfunctions are identified. Cytoreduction should also be given to ET patients with progressive thrombocytosis (>800x109U/L) to avoid massive stroke and acute myocardial infarction except for those with prefibrotic primary myelofibrosis.

For patients with intermediate and high-risk ET, aspirin and the addition of HU or PEG-INFα 2A/2B or adjunct anagrelide can be given for cytoreduction. Cardiovascular risk factors and the presence of new thrombosis or acquired vWD should be monitored. When using HU, Dr. Gill noted that the prolonged use of HU is associated with increased risk of skin cancer and should be avoided. Also, ruxolitinib is not recommended as it is off-label for this population.

For patients with myelofibrosis (MF), although both the mutation-enhanced IPSS (MIPSS70+) and the genetically-inspired International Prognostic Scoring System (GIPSS) model algorithms recommend allogeneic hematopoietic stem-cell transplantation (HSCT) in high and very-high risk eligible patients, Dr. Gill stated that these patients are estimated to have a low 5-year post-HSCT overall survival (OS) of 37% and 22%, respectively, by the myelofibrosis transplant scoring system (MTSS).1 On the other hand, high and very-high risk patients who did not underwent HSCT are predicted to have a 5-year OS of 50% and 34%, respectively, indicating that HSCT is unlikely to provide a positive benefit-risk and should only be considered for those with low or intermediate-risk when specific indication is available.2 That said, patients with low and intermediate-risks should be given treatment according to symptom needs. In fact, very-low risk patients can be placed in observation, enrolled to clinical trials or given HU or PEG-INFα 2A/2B if cytoreduction is needed.

Lastly, MF patients who have anemia can be managed by erythropoietin and erythropoietin-stimulating agents (ESA). Thalidomide monotherapy can be considered and is typically given as a single-agent therapy as prednisolone is associated with an increased risk of infection. Lenalidomide is generally not recommended due to its myelosuppressive effect that can induce cytopenia. Danazol is also not recommended as it is associated with very low response rates and disfigurement among women. When considering the management options for anemic MF patients, Dr. Gill reiterated that a well-organized transition program is necessary, “If a MPN patient is deemed transfusion-dependent, we should transfuse them well and chelate them well.”

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