Dr. Verstovsek on the MANIFEST Trial With CPI-0610 in Myelofibrosis

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Srdan Verstovsek, MD, PhD, discusses the phase 2 MANIFEST study, which examined CPI-0610 as an “add-on” to ruxolitinib in patients with myelofibrosis.

Srdan Verstovsek, MD, PhD, the United Energy Resources, Inc. Professor of Medicine; director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms; and chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the phase 2 MANIFEST study, which examined CPI-0610 as an “add-on” to ruxolitinib (Jakafi) in patients with myelofibrosis.

In the second-line setting, following ruxolitinib, patients with myelofibrosis have more advanced features, with lower platelets and more anemia, says Verstovsek; these patients might also be more genetically complex. In that setting, medications are expected to be effective because of the acquisition of epigenetic abnormalities; that was the initial intent of the study, adds Verstovsek.

Some activity was reported with CPI-0610 as a single agent in the second-line setting. For example, patients experienced immune responses, improvements in quality of life, and an occasional improvement in white blood cell count. Modest improvements with a single agent in a complex disease were observed in this study, says Verstovsek. Further research is needed because the number of participants included in the study were small.

Patient characteristics can affect the delivery of the drug, adds Verstovsek; the agent can cause myelosuppression if it is not carefully delivered. The drug is delivered 2-weeks-on/1-week-off in an effort to prevent the occurrence of thrombocytopenia. Some gastrointestinal toxicity has also been observed with the agent, concludes Verstovsek.

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