After Progression on Ruxolitinib, BETi Provides Significant Benefit for Myelofibrosis

By Annette M. Boyle, /alert Contributor
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In a phase II study, a bromodomain and extraterminal protein inhibitor (BETi) reduced anemia, spleen volume and symptoms in myelofibrosis patients who had progressed on ruxolitinib, according to research presented at the American Society of Clinical Oncology 2019 Annual Meeting in Chicago by Marina Kremyanskaya, MD, PhD, assistant professor of hematology and medical oncology at the Mount Sinai School of Medicine in New York.

Previous studies indicate that BETi may work synergistically with ruxolitinib to reduce splenomegaly, bone marrow fibrosis and malignant allele burden in patients with myelofibrosis.


Patient talking with doctor. Source: Getty

Researchers evaluated the oral BETi CPI-0610 in a three arm study. 

The first two arms enrolled patients with myelofibrosis who had progressed on ruxolitinib. At the time of the report, Arm 1 had treated four patients with CPI-0610 monotherapy, two of whom were transfusion dependent at baseline. Arm 2 had enrolled 14 patients to receive CPI-0610 combined with ruxolitinib. 

The planned third arm will treat JAK inhibitor-naïve patients with a combination of CPI-0610 and ruxolitinib. It has not yet accrued any patients.

The median age of enrolled patients was 69 and nine were male. The participants had a mutational burden, with 17 of 18 total having JAK2/MPL/CALR mutations and 10 having three or more mutations. Eleven participants had received at least one line of therapy other than ruxolitinib. At baseline, 11 patients had hemoglobin of less that 10 g/dL.

Two transfusion dependent patients in Arm 2 became transfusion independent and both continue on the combined ruxolitinib/CPI-0610 therapy without transfusions. 

Both of the patients with anemia in Arm 1 and three of the nine anemic patients in Arm 2 experienced a hemoglobin increase of at least 1.5 g/dL from baseline over successive cycles of therapy. 

In all 10 evaluable patients, magnetic resonance imaging revealed spleen volume reduction, ranging from 6% to 44%. Spleen volume decline regardless of the patients’ driver mutations. The researchers also noted that patients experienced improvement in symptoms and reductions of cytokine levels.

In Arm 1, both evaluable patients saw improvement in marrow fibrosis as well as an increase in hemoglobin. They both also experienced resolution of thrombocytosis.

 

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