Maximizing the Management of MPNs

January 13, 2021 - Defining treatment goals for patients with myeloproliferative neoplasms is critical in order to optimize therapy, even if the dominant concern is disease progression.

Defining treatment goals for patients with myeloproliferative neoplasms (MPNs) is critical in order to optimize therapy, even if the dominant concern is disease progression, said Elizabeth Hexner, MD, MSTR, in a presentation during a 2020 Institutional Perspectives in Cancer webinar on hematologic malignancies.

Delineating Treatment Goals

MPNs are comprised of 4 distinct diseases––essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), and accelerated or blast phase MPN––each of which should be grouped into categories based on the goals of treatment (Table).1

Table: Treatment Goals in Each MPN

For patients with ET, the primary concern is vascular risk reduction, for which low-dose aspirin is given. If patients are high risk according to the International Prognostic Score for Thrombosis in Essential Thrombocythemia risk score, cytoreduction with hydroxyurea can be considered, said Hexner.

“This is a population with a normal life expectancy, so I’m not trying to add a lot of new medication to this group of patients,” said Hexner.

Symptoms of PV are often more apparent than those in ET, presenting as itchiness and sweats or headaches and visual symptoms, said Hexner. In the case of uncontrollable symptoms, ruxolitinib (Jakafi) can be considered.

Patients with MF who are experiencing spleen-related or constitutional symptoms are “often well addressed” with ruxolitinib or fedratinib (Inrebic).

The latter JAK inhibitor was approved by the FDA in August 2019 for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-PV or post-ET) myelofibrosis.2

The approval is based on findings from the phase 3 JAKARTA study, which evaluated fedratinib in patients with primary or secondary MF; results demonstrated a significant reduction in splenomegaly and symptom burden in patients with MF.

For patients whose primary concern is anemia, luspatercept (Reblozyl) could be an option worth considering. Although not yet approved, the agent led to increased hemoglobin and decreased red blood cell transfusion in findings from a phase 2 study of non-transfusion dependent and transfusion-dependent patients with MF-associated anemia, respectively.3

Traditionally, JAK inhibitors are continued for patients who progress to accelerated or blast phase, said Hexner. However, findings from a phase 2 study presented at the 2020 ASH Annual Meeting & Exposition indicated that the addition of decitabine to ruxolitinib led to an objective response rate of 44% and a median overall survival of 9.5 months, which compares favorably with more intensive chemotherapy regimens, added Hexner.4

Considering COVID-19

Despite the potential synergy of MPNs and coronavirus disease 2019 (COVID-19), which are both prothrombotic, patients with MPNs are not necessarily at higher risk for developing the virus, explained Hexner. Rather, age and comorbidities should be used to determine individual risk.

In terms of treatment adaptations, there is “really no evidence to support alterations to our therapeutics interventions in MPN,” said Hexner.

Although phlebotomy had been deferred at the start of the pandemic, it has since resumed, explained Hexner, now that the risks of deferring medical visits outweigh the risks of contracting the virus. 

“There has been a lot of interest in JAK inhibition as an anti-cytokine therapy for the treatment of moderate to severe COVID-19, but it’s not a reason to start it in MPN patients,” concluded Hexner. “If patients develop COVID-19, they should continue their JAK inhibitor.”


  1. Hexner E. Myeloproliferative neoplasms: what’s new? Presented at: 2020 Institutional Perspectives in Cancer webinar on hematologic malignancies. Accessed January 5, 2020.
  2. U.S. FDA approves INREBIC (fedratinib) as first new treatment in nearly a decade for patients with myelofibrosis. Celgene Corporation. Published August 16, 2019. Accessed August 16, 2019.
  3. Gerds AT, Vannucchi AM, Passamonti F, et al. A phase 2 study of luspatercept in patients with myelofibrosis-associated anemia. Blood. 2019;134(suppl 1):557. doi:10.1182/blood-2019-122546
  4. Mascarenhas JO, Rampal RK, Kosiorek HE, et al. Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase. Blood Adv. 2020;4(20):5246-5256. doi:10.1182/bloodadvances.2020002119


Which of the following is true?

TP53 mutations in MPN progressed to accelerated or blast phase disease: