Lucia Masarova, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of ropeginterferon alfa-2b-njft (Besremi) in adult patients with essential thrombocythemia, highlighting the unmet needs that investigators aim to address with this investigation.

Data from the phase 2 EXCEED-ET trial (NCT05482971) of ropeginterferon alfa were presented by investigators at the 2023 ASCO Annual Meeting. To address unmet needs that are present in the treatment of adult patients with essential thrombocythemia, investigators launched the ongoing, single-arm, multicenter trial to assess the efficacy, safety, and tolerability of ropeginterferon alfa. All patients are to be treated with ropeginterferon alfa, which is an injectable agent, Masarova says. This agent will be given at a faster dose escalation than normally conducted in this population, Masarova adds. This agent is given every other week, starting with 250 μg, then 350 μg, and 500 μg as the maximum dose, she says, adding that patients will then stay on treatment for up to 56 weeks. The investigators will then measure control of the platelet counts.

Patients with newly diagnosed essential thrombocythemia or patients whose essential thrombocythemia failed to respond to hydroxyurea and who still have palpable disease or treatable symptoms are eligible to enroll in the trial, she expands. Moreover, the major primary end point of the trial is durability of response. The investigators will measure hematologic response, such as platelet count remission. Key secondary end points will include hematologic response, control of spleen, and occurrence of thromboembolic events, she adds.

Interestingly, patients pretreated with an interferon are not eligible for the current study, but future amendments to the study will include mandatory measurement of neutralizing antibodies. Upon this amendment, patients who carry no neutralizing antibodies will be eligible regardless of previous interferon exposure, Masarova concludes.

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Lucia Masarova, MD, discusses the investigation of ropeginterferon alfa in adult patients with essential thrombocythemia, highlighting the unmet needs that investigators aim to address with this investigation.


Dr Masarova on the Investigation of Ropeginterferon Alfa in Essential Thrombocythemia

Lucia Masarova, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the single-arm multicenter phase 2 EXCEED-ET trial (NCT05482971) of ropeginterferon alfa-2b-njft (Besremi) in adult patients with essential thrombocythemia.

At the 2023 ASCO Annual Meeting, Masarova and colleagues overviewed information from the ongoing phase 1/2 EXCEED-ET trial (NCT05482971) evaluating the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft in adult patients with essential thrombocythemia.

Pegylated interferons have been utilized in the treatment of patients with essential thrombocythemia and polycythemia vera over the past few decades, Masarova notes. These types of agents of interest for the treatment of patients in these populations due to possible disease-altering activity observed with their use, she adds, noting that interferons have the ability to attack the malignant clones of the disease.

Ropeginterferon alfa-2b-njft was previously approved by the FDA in November 2021 for use as a treatment in patients with polycythemia vera. The rationale for EXCEED-ET is to potentially bring the compound to patients with essential thrombocythemia, Masarova concludes.

The study is enrolling patients with essential thrombocythemia who are naïve to cytoreductive treatments, or who are pre-exposed to hydroxyurea or anagrelide. They also need to have a platelet count of at least 450 x 109/L at screening. Patients are receiving ropeginterferon alfa-2b-njft subcutaneously starting at 250 µg at week 0, 350 µg at week 2, and 500 µg at week 4. The agent is then continued at 500 µg every 2 weeks for up to 56 weeks.

Lucia Masarova, MD, discusses the single-arm multicenter phase 2 EXCEED-ET trial of ropeginterferon alfa-2b-njft in adult patients with essential thrombocythemia.


Dr Masarova on the Rationale for Investigating Ropeginterferon Alfa-2b in Essential Thrombocythemia

Lucia Masarova, MD, an assistant professor in the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses future research ​efforts in myeloproliferative neoplasms (MPNs).

With multiple encouraging studies and investigational agents in the pipeline, the MPN space ​appears to be entering an exciting era, says Masarova.

Notably, the field is anticipating additional data with other JAK inhibitors ​beyond ruxolitinib (Jakafi) and fedratinib (Inrebic), ​Masrova explains.

Additionally, findings regarding targeted agents and novel combination therapies ​with JAK inhibitors ​are poised to read out at a future medical meeting, Masrova concludes.

Lucia Masarova, MD, discusses future research ​efforts in myeloproliferative neoplasms. 

Dr. Masarova on Future Research in MPNs 

Lucia Masarova, MD, an assistant professor in the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the toxicities associated with the combination of JAK inhibitors and other targeted therapies in patients with myelofibrosis.

The main challenge with combining targeted therapies with JAK inhibitors in myelofibrosis are the toxicities, says Masarova. Toxicities are a concern, especially with regard to myelosuppression. It can be difficult to understand the reason why some patients lose response or achieve suboptimal response; it could be because the ruxolitinib (Jakafi) has failed or because another agent has been added, explains Masarova.

The toxicities with these combinations have been as expected, despite concerns regarding thrombocytopenia when agents like navitoclax are added to ruxolitinib. However, this toxicity has been found to be well managed, concludes Masarova.

Lucia Masarova, MD, discusses the toxicities associated with the combination of JAK inhibitors and other targeted therapies in patients with myelofibrosis.

Lucia Masarova, MD

Articles

Dr Masarova on the Investigation of Ropeginterferon Alfa in Essential Thrombocythemia

Dr Masarova on the Rationale for Investigating Ropeginterferon Alfa-2b in Essential Thrombocythemia

Dr. Masarova on Future Research in MPNs

Dr. Masarova on the Safety of JAK Inhibitor/Targeted Therapy Combos in Myelofibrosis