One emerging hypothesis is that combining the JAK2 inhibitor ruxolitinib with HSP90 inhibitors may increase the efficacy of myelofibrosis treatment. To test this hypothesis, a team of investigators treated mice that had myelofibrosis with the investigational combination therapy, comparing their results to control groups treated with ruxolitinib alone or PU-H71 alone. They also assessed the effects of adding PU-H71 treatment as a second therapy to mice already being treated with ruxolitinib. Study endpoints included reduction in white blood cell count, platelet count, and spleen weight; reduction in JAK2 protein levels in the blood, spleen, and bone marrow; and presence of scar tissue in the bone marrow.
In this study, researchers observed that mice that had been treated with the combination therapy had a more significant reduction in white blood cell count, platelet count, and spleen weight after 14 days of therapy. The benefits of combination therapy versus ruxolitinib alone were even more significant after 29 days of treatment. The combination therapy was also associated with a reduction in bone marrow scar tissue and a reduction in the activity of the JAK2 pathway. Comparable effects were also observed in mice that were treated with PU-H71 plus ruxolitinib after initial monotherapy with ruxolitinib, further demonstrating the efficacy of combination treatment. Most importantly, in those mice treated with combination ruxolitinib and PU-H71 therapy, investigators observed a decrease in JAK2 levels, revealing that PU-H71 may prevent or reverse the increases in JAK2 protein levels seen with chronic ruxolitinib therapy. Of note, combination treatment was well tolerated and not associated with increased side effects compared to either therapy alone.
"Now that we have found a way to combat the treatment resistance commonly seen in myelofibrosis, we are continuing these trials with the hope that these results will one day provide a treatment
|Contact: Andrea Slesinski|
American Society of Hematology