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Dr Zhou on the Use of Combination Therapies in Myelofibrosis

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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.

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.

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