Raajit K. Rampal, MD, PhD

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.

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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.

Author | Raajit K. Rampal, MD, PhD

Articles

Dr. Rampal on Investigational Agents in MPNs

Dr. Rampal on Ongoing Research With Pacritinib in Myelofibrosis

Dr. Rampal on Unmet Needs in Myelofibrosis and Polycythemia Vera

Dr. Rampal on Treatment Options in Polycythemia Vera