BET Inhibitor CPI-0610 Shows Potential as Treatment in Myelofibrosis


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 efficacy of CPI-0610 in the phase 2 MANIFEST (NCT02158858) trial in patients with myelofibrosis.

Masarova says that CPI-0610, a bromodomain, and extra-terminal (BET) inhibitor holds promise in patients with myelofibrosis since it could alter the transcription factors and potentially overcome the patient’s resistance to ruxolitinib (Jakafi). The MANIFEST trial investigating this drug had 3 arms; the second arm combined ruxolitinib and CPI-0610 in patients who responded suboptimally to ruxolitinib monotherapy and the third looked at the combination in the front-line setting.

For Arm 2, there were 70 patients enrolled and median follow-up of 28 weeks. There were 64 patients enrolled and median follow-up of 24 weeks in Arm 3. The second arm showed that patients could achieve further improvement in their spleen or their symptoms when receiving CPI-0610 in addition to ruxolitinib. The upfront combination in previously untreated patients demonstrated superior responses in terms of spleen size and symptoms. Spleen volume reduction was seen in about 60% of these patients, which is more than what is observed in the single-agent ruxolitinib trials, according to Masarova.

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