Prithviraj Bose, MD, an associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses current treatment options for essential thrombocythemia (ET).

The majority of the field uses hydroxyurea (Hydrea) for high-risk patients with ET and possibly intermediate-risk patients, says Bose. Available data support the use of this agent in this patient population, adds Bose. Interferons are also used in certain centers and are another very reasonable treatment option, according to Bose.

The JAK inhibitor ruxolitinib (Jakafi) was also approved by the FDA for the treatment of patients with myelofibrosis but is currently under development in ET, concludes Bose.

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Prithviraj Bose, MD, discusses current treatment options for essential thrombocythemia.

Dr. Bose on Current Treatment Options for Essential Thrombocythemia

Prithviraj Bose, MD, an associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses novel agents under investigation in essential thrombocythemia (ET).

While new mechanisms of action are under exploration, there have not been too many developments in ET, says Bose. Currently, the challenge in this disease is that  because survival is so good, drug development is not as much of an unmet need compared with other cancers that have a much worse prognosis. 

However, some unmet needs do exist. For example, current therapies are unable to address symptoms of disease well. That is why ruxolitinib (Jakafi) would make a very important difference in the field, according to Bose. 

Additionally, there is now interest in examining ropeginterferon alfa-2b, which has the trade name of Besremi in Europe, where it was approved in the beginning of 2019 for use in patients with polycythemia vera. There is interest in exploring the drug in patients with ET, with 1 trial having been publicly, Bose added. This could serve as a novel treatment for patients with ET, as interferons can yield deep molecular responses, explains Bose. The agent will be given every 2 weeks initially and then every 4 weeks, which could be beneficial for patients with 

Prithviraj Bose, MD, discusses novel agents under investigation in essential thrombocythemia.

Dr. Bose on Novel Agents Under Investigation in Essential Thrombocythemia

Prithviraj Bose, MD, associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses management strategies for patients with myelofibrosis who progress on ruxolitinib (Jakafi).

Finding appropriate approaches to manage patients who progress on ruxolitinib has proven to be very difficult, says Bose. Prior to the August 2019 FDA approval of the JAK inhibitor fedratinib (Inrebic), these patients had limited treatment options. 

When ruxolitinib failed, hydroxyurea was used to control counts, and danazol was used to improve hemoglobin in these patients, says Bose. Thalidomide (Thalomid) or lenalidomide (Revlimid) were also appropriate to use. Immunomodulatory drugs that used to be very popular prior to ruxolitinib have also been utilized in this setting, adds Bose.

Another approach that is sometimes used consists of stopping ruxolitinib for some time and then re-starting patients on the agent. Re-challenging patients with the agent was another approach used prior to the approval of fedratinib, concludes Bose.

Prithviraj Bose, MD, discusses management strategies for patients with myelofibrosis who progress on ruxolitinib (Jakafi).

Dr. Bose on the Management of Patients With Myelofibrosis Who Progress on Ruxolitinib

Prithviraj Bose, MD, associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses management strategies for patients with myelofibrosis who progress on ruxolitinib (Jakafi).

Finding appropriate approaches to manage patients who progress on ruxolitinib has proven to be very difficult, says Bose. Prior to the August 2019 FDA approval of the JAK inhibitor fedratinib (Inrebic), these patients had limited treatment options.

When ruxolitinib failed, hydroxyurea was used to control counts, and danazol was used to improve hemoglobin in these patients, says Bose. Thalidomide (Thalomid) or lenalidomide (Revlimid) were also appropriate to use. Immunomodulatory drugs that used to be very popular prior to ruxolitinib have also been utilized in this setting, adds Bose.

Another approach that is sometimes used consists of stopping ruxolitinib for some time and then re-starting patients on the agent. Re-challenging patients with the agent was another approach used prior to the approval of fedratinib, concludes Bose.

Prithviraj Bose, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the utility of ruxolitinib (Jakafi) in patients with myelofibrosis.

Ruxolitinib is a JAK1/2 inhibitor that has been around for close to 9 years, says Bose. It is a good drug for reducing splenomegaly and improving symptoms. The drug leads to improved quality of life (QOL) for patients with myelofibrosis and MPNs. Additionally, long-term follow-up from the COMFORT trials show that there is a survival benefit with ruxolitinib which is thought to be an indirect result of improved QOL, says Bose.

However, one of the drawbacks of ruxolitinib is that the agent can lead to a drop in hemoglobin and platelet counts within the first 12 to 24 weeks of treatment, leading to treatment discontinuation in some cases, concludes Bose.

Prithviraj Bose, MD, discusses the utility of ruxolitinib in patients with myelofibrosis.

Dr. Bose on the Utility of Ruxolitinib in Myelofibrosis

Prithviraj Bose, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses novel agents under investigation in myelofibrosis.

Novel agents are being studied in combination with ruxolitinib (Jakafi) and as single agents after JAK inhibitor failure, says Bose. CPI-0610, which is a bromodomain inhibitor, and navitoclax, which is a BCL-2/BCXL antagonist, have shown the most potential in combination with ruxolitinib.

Imetelstat, which is being studied as a single agent post-ruxolitinib, has shown evidence of a survival advantage. Because the drug wasn’t compared with an active agent, it's difficult to determine whether the agent has a real survival advantage, says Bose. However, in comparison to historical controls, it looks like it does.

PRM-151, is an anti-fibrotic drug that’s under investigation. The field also has preliminary data with the LSD1 inhibitor bomedemstat. All of these agents are active, and more data regarding these drugs are expected to be presented during the 2020 European Hematology Association Virtual Congress, concludes Bose.

Prithviraj Bose, MD, discusses novel agents under investigation in myelofibrosis.

Dr. Bose on Novel Agents Under Investigation in Myelofibrosis

Prithviraj Bose, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses novel agents under investigation in myelofibrosis.

Novel agents are being studied in combination with ruxolitinib (Jakafi) and as single agents after JAK inhibitor failure, says Bose. CPI-0610, which is a bromodomain inhibitor, and navitoclax, which is a BCL-2/BCXL antagonist, have shown the most potential in combination with ruxolitinib.

Imetelstat, which is being studied as a single agent post-ruxolitinib, has shown evidence of a survival advantage. Because the drug wasn’t compared with an active agent, it's difficult to determine whether the agent has a real survival advantage, says Bose. However, in comparison to historical controls, it looks like it does.

PRM-151, is an anti-fibrotic drug that’s under investigation. The field also has preliminary data with the LSD1 inhibitor bomedemstat. All of these agents are active, and more data regarding these drugs are expected to be presented during the 2020 European Hematology Association Virtual Congress, concludes Bose.

Prithviraj Bose, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses treatment for patients with progressive myelofibrosis.

The revised International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria released in 2013 provide insight on splenic progression and leukemic transformation, says Bose. 

However, patients can progress in many ways. This makes treating patients with other symptoms of progression challenging. Patients who progress may have spleen growth, worsening symptoms, increased anemia or thrombocytopenia, elevated white blood cell counts, and go into accelerated blast phase, says Bose. These symptoms may present individually or in combination. 

Though ruxolitinib (Jakafi) is the frontline standard of care for patients with myelofibrosis, many patients require an alternative therapy upon progression, says Bose. Notably, in August 2019, the FDA approved fedratinib (Inrebic) for the treatment of patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. This may provide an option for patients who progress on ruxolitinib.

Prithviraj Bose, MD, discusses treatment for patients with progressive myelofibrosis.

Prithviraj Bose, MD

Articles

Dr. Bose on Current Treatment Options for Essential Thrombocythemia

Dr. Bose on Novel Agents Under Investigation in Essential Thrombocythemia

Dr. Bose on the Management of Patients With Myelofibrosis Who Progress on Ruxolitinib

Dr. Bose on the Management of Patients With Myelofibrosis Who Progress on Ruxolitinib

Dr. Bose on the Utility of Ruxolitinib in Myelofibrosis

Dr. Bose on Novel Agents Under Investigation in Myelofibrosis

Dr. Bose on Novel Agents Under Investigation in Myelofibrosis

Dr. Bose on Treating Progression in Patients With Myelofibrosis