Raajit K. Rampal, MD, PhD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, discusses available tools to estimate prognosis in myelofibrosis.

The field has to be careful with regard to prognostication, says Rampal. Prognostication may depend on the specific allele burden or other co-mutations; however, tools are available to help address these challenges. One tool is called the Mutation-Enhanced International Prognostic Scoring System 70+ v2.0, which is for primary myelofibrosis; this is a calculator. Clinical variables and mutations are inputted into the tool, which will then compute the patient’s overall survival at 5 or 10 years.

Other scoring systems exist, such as the Genetically Inspired Prognostic Scoring System, which is also a genetic prognostic scoring tool. The MYSEC Prognostic Model Risk Calculator is another tool for secondary myelofibrosis. The field has interesting tools that can be used in clinical practice that utilize genomics, according to Rampal. Another scoring system can be used for transplant; it predicts how well a patient is likely to do with transplant based on their mutations, explains Rampal.

The 2 major points are that mutation profiles have a clear clinical impact in terms of prognostication, as well as clinical practice in terms of which patients are at a higher risk. These prognostications have implications for how patients with myelofibrosis are treated, concludes Rampal.

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Raajit K. Rampal, MD, PhD, discusses available tools to estimate prognosis in myelofibrosis.

Dr. Rampal on Tools to Estimate Prognosis in Myelofibrosis

Raajit K. Rampal, MD, PhD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, discusses challenges with targeting high-risk mutations in patients with myelofibrosis.

One challenge in the field of myelofibrosis is that oftentimes, drugs are not available for the targets identified, says Rampal. 

is prevalent in patients who have more advanced disease, as well as those whose disease transforms to acute myeloid leukemia (AML) from myelofibrosis. Two inhibitors for 

mutations have been approved by the FDA. One clinical trial is examining the combination of ruxolitinib (Jakafi) and enasidenib (Idhifa); that is an MPN Research Consortium trial, Rampal adds.

The field will have to wait and see what happens but there are already data showing that targeting

 in patients who transformed to AML from myeloproliferative neoplasm can have efficacy. Effective drugs are not yet available for the other high-risk mutations, such as 

, says Rampal. Splicing factor mutations are being investigated in clinical trials; targeting these mutations might be the next big focus with regard to research, as they appear to be associated with poor prognosis, concludes Rampal.

Raajit K. Rampal, MD, PhD, discusses challenges with targeting high-risk mutations in patients with myelofibrosis.

Dr. Rampal on Challenges With Targeting High-Risk Mutations in Myelofibrosis

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the evolving understanding of genetic alterations in myeloproliferative neoplasms (MPNs).

Aside from the principle driver mutations, research efforts have begun to home in on the role of other mutations in patients with MPNs, Rampal explains.

, and those in the RAS pathway, appear to confer a worse prognosis in patients with myelofibrosis, says Rampal.

Additionally, some evidence  suggests that the presence of splicing factor mutations in patients with polycythemia vera or essential thrombocythemia is associated with a higher risk of progressing to myelofibrosis, Rampal explains. 

Understanding the role of these genomic alternations may inform prognosis, as well as introduce the possibility of targeting these mutations therapeutically, which has not yet been done, Rampal concludes.

Raajit K. Rampal, MD, PhD, discusses the evolving understanding of genetic alterations in myeloproliferative neoplasms.  



Dr. Rampal on the Evolving Understanding of Genomic Alterations in MPNs 

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses investigational agents in myeloproliferative neoplasms (MPNs).

The MDM2 inhibitor idasanutlin (RG7388) is being looked at in an ongoing phase II trial (NCT03287245) to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of the agent for the treatment of patients with polycythemia vera who are resistant to or intolerant of hydroxyurea. Idasanutlin demonstrated promising preclinical and phase I clinical trial (NCT02407080) activity for this patient population, says Rampal.

In myelofibrosis, the August 2019 approval of fedratinib (Inrebic) was a revolutionary addition to the armamentarium, explains Rampal.

Other investigational compounds in myelofibrosis are currently being explored in clinical trials, concludes Rampal.

Raajit K. Rampal, MD, PhD, discusses investigational agents in myeloproliferative neoplasms.

Dr. Rampal on Investigational Agents in MPNs

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses ongoing research with pacritinib in myelofibrosis.

Several JAK inhibitors are in development in myelofibrosis, one of which is pacritinib. Pacritinib is under evaluation, specifically in patients with myelofibrosis who have low platelets, says Rampal. A study evaluating the use of pacritinib was recently completed, and data from that trial are anticipated to read out in the near future.

In addition, there is a planned phase III trial that will look at pacritinib versus investigator’s choice for patients with low platelets. This will be an important study, if positive, because there is currently no standard of care for patients with platelets below 50,000 per microliter, concludes Rampal.

Dr. Rampal on Ongoing Research With Pacritinib in Myelofibrosis

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses unmet needs in the treatment of patients with myelofibrosis and polycythemia vera.

In 2011, the JAK1/2 inhibitor ruxolitinib (Jakafi) became the first approved agent designed to treat patients with myelofibrosis. In 2014, ruxolitinib became the first drug to receive regulatory approval for the treatment of patients with polycythemia vera. In August 2019, fedratinib (Inrebic), a JAK2 inhibitor, was approved for the treatment of patients with intermediate-2 or high-risk primary or secondary myelofibrosis.

Beyond these agents, there are few options that are available to patients, explains Rampal. About half of patients with myelofibrosis who are treated with ruxolitinib will progress within 1.5 to 3 years. Similarly, response rates could decrease over time for patients with polycythemia vera who are treated with ruxolitinib.

Therefore, clinical trials should be considered for patients with either myelofibrosis or polycythemia vera who progress on these agents, concludes Rampal.

Raajit K. Rampal, MD, PhD, discusses unmet needs in the treatment of patients with myelofibrosis and polycythemia vera.

Dr. Rampal on Unmet Needs in Myelofibrosis and Polycythemia Vera

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses treatment options in polycythemia vera.

Initially, a patient should be evaluated to determine if they require pharmacologic treatment, explains Rampal.

Upfront treatment for patients who require therapy includes hydroxyurea and interferon. Long-term data suggests both agents are active in this space, says Rampal. Additionally, there is emerging data that ropeginterferon alfa-2b is another active agent in the frontline setting.

Patients who fail treatment with hydroxyurea should be considered for second-line therapywith the JAK1/2 inhibitor ruxolitinib (Jakafi). In later-line settings, investigational therapies are currently being explored, concludes Rampal.

Raajit K. Rampal, MD, PhD

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