Amy W. Zhou, MD, assistant professor, Department of Medicine, Division of Hematology, Washington University School of Medicine in St. Louis, discusses ongoing and planned trials that may enhance therapeutic options for patients with myelofibrosis and anemia that are currently taking place at the Washington University School of Medicine in St. Louis.

The team at Washington University School of Medicine in St. Louis is presently involved in a phase 1/2 clinical trial (NCT04455841), Zhou begins. This open-label, dose-finding study is designed to assess the efficacy and safety profile of the ALK2 inhibitor INCB000928, both as a standalone therapy and in combination with ruxolitinib (Rituxan), for patients with myelofibrosis who have symptomatic anemia or are transfusion dependent, she explains. This trial will evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of INCB000928.

Investigators have also launched another phase 1b/2a open-label clinical study (NCT05320198), Zhou expands. This investigation focuses on the utilization of DISC-0974, an agent with anti-hemojuvelin properties that is known to effectively mitigate hepcidin levels, in patients with myelofibrosis and anemia, she emphasizes. This trial will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of DISC-0974 as well as categorize its effects on anemia response in participants with myelofibrosis and anemia. This novel treatment approach holds promise for patients, potentially bringing forth a new era of management strategies for this challenging disease, Zhou states.

As the horizon of hematology research broadens, Zhou underscores the importance of these ongoing trials, particularly as some of the investigational treatments are poised for potential FDA approval. These research initiatives illuminate the commitment of investigators as they further evaluate potential therapeutic options for patients grappling with myelofibrosis-related anemia, she states. These clinical trials aim to alleviate the burden of myelofibrosis and provide hope for patients seeking improved treatment outcomes for their disease, Zhou concludes.

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Amy W. Zhou, MD, discusses ongoing and planned trials that may enhance therapeutic options for patients with myelofibrosis and anemia that are currently taking place at the Washington University School of Medicine in St. Louis.


Dr Zhou on Ongoing Investigations into the Treatment of Patients With Myelofibrosis and Anemia

Amy W. Zhou, MD, assistant professor, Department of Medicine, Division of Hematology, Washington University School of Medicine in St. Louis, discusses combination therapies with ruxolitinib (Jakafi) that may contribute to the treatment paradigm for patients with myelofibrosis, highlighting the importance of continued research with phase 3 confirmatory trials for patients with this disease.

Several combination therapies that are being evaluated in the treatment armamentarium of myelofibrosis integrate the agent pelabresib (CPI-0610), Zhou begins. These include the regimen assessed in the phase 2 MANIFEST trial (NCT02158858), where researchers are exploring the use of pelabresib as an upfront therapy alongside treatment with ruxolitinib, she says. Furthermore, the randomized, placebo-controlled phase 3 MANIFEST-2 study (NCT04603495) will reveal whether this combination approach is more effective than treatment with ruxolitinib alone in patients with treatment-naïve disease, Zhou notes. Data from phase 2 studies indicate that pelabresib may play a vital role in the treatment of patients who become refractory to or lose progress on their treatment with ruxolitinib, she emphasizes.

Previous research shows that the addition of pelabresib to ruxolitinib may lead to enhanced spleen and symptom responses in patients with myelofibrosis, Zhou expands. This combination offers promise for patients who didn't achieve optimal responses with JAK inhibitors, she explains. Regarding the application of these combinations in the frontline setting, oncologists continue to await the results of the MANIFEST-2 study, she adds. Phase 3 data are crucial for establishing whether the efficacy of combination therapy surpasses that of single-agent treatment, Zhou says.

The expanding array of therapeutic agents for managing myelofibrosis with anemia is a source of excitement, particularly as it addresses an area of unmet medical need, she continues. The emergence of additional treatment options for patients with myelofibrosis is promising, and these therapies will hopefully gain FDA approval to assist this patient population, she concludes.

Amy W. Zhou, MD, discusses combination therapies with ruxolitinib that may contribute to the treatment paradigm for patients with myelofibrosis, highlighting the importance of continued research with phase 3 confirmatory trials for patients with this disease.


Dr Zhou on the Use of Combination Therapies in Myelofibrosis

Amy W. Zhou, MD, assistant professor, Department of Medicine, Division of Hematology, Washington University School of Medicine in St. Louis, discusses the investigation of ruxolitinib (Jakafi) given in conjunction with novel or emerging agents such as pacritinib (Vonjo) and momelotinib (Ojjaara), highlighting these agents’ potential at contributing to the treatment paradigm in myelofibrosis.

Combination therapies involving ruxolitinib are demonstrating the potential for anemia improvement in patients with myelofibrosis, Zhou begins. Although the superiority of these JAK inhibitor combinations when compared with single-agent ruxolitinib has not yet been conclusively determined, data from phase 2 investigations indicates that pelabresib (CPI-0610) may be an effective option for patients who are refractory or lose response to ruxolitinib, she says.

The addition of pelabresib to ruxolitinib was evaluated as an upfront therapy in the phase 2 MANIFEST trial (NCT02158858), Zhou details. This global, open-label, nonrandomized, multicohort study was designed to ascertain whether this JAK inhibitor combination therapy was more effective than ruxolitinib monotherapy for patients with JAK inhibitor-pretreated or JAK inhibitor-naïve myelofibrosis.

Initial findings from the JAK inhibitor-naïve cohort demonstrated that pelebresib and ruxolitinib elicited a reduction of spleen volume by 35% in 68% of individuals. This was accompanied by a decrease in the total symptom score by at least 50% in 56% of participants at the 24-week mark.

The augmented spleen and symptom responses achieved with pelabresib and ruxolitinib indicate that JAK inhibitor combination therapies may be a viable option for patients who have not yet achieved an optimal response with JAK inhibitor monotherapy, Zhou states. However, the eventual integration of these combination therapies into the frontline setting hinges on the results of phase 3 trials such as the MANIFEST-2 trial (NCT04603495), she notes. This study is evaluating the use of upfront pelabresib and ruxolitinib vs ruxolitinib alone in a larger cohort of patients with JAK inhibitor-naïve myelofibrosis.

Trials like MANIFEST-2 will provide essential comparisons through rigorous, randomized, controlled investigations, thereby more definitively determining whether the combination approach surpasses the efficacy of a single-agent JAK inhibitor in the management of patients with myelofibrosis, Zhou concludes.

Amy W. Zhou, MD, discusses the investigation of ruxolitinib given in conjunction with novel or emerging agents such as pacritinib and momelotinib, highlighting these agents’ potential at contributing  to the treatment paradigm in myelofibrosis.
  

Amy W. Zhou, MD

Articles

Dr Zhou on Ongoing Investigations into the Treatment of Patients With Myelofibrosis and Anemia

Dr Zhou on the Use of Combination Therapies in Myelofibrosis

Dr Zhou on the Evaluation of Combination Therapies With Ruxolitinib in Myelofibrosis