The breast cancer drug palbociclib may be able to treat myelofibrosis either alone or in combination with ruxolitinib.
Palbociclib, a drug used to treat certain advanced breast cancers, may be a new treatment option for myelofibrosis, according to research published in Cancer Research.
Myelofibrosis is a form of leukemia that affects 1 to 1.5 of every 100,000 people. Current treatments do not address bone marrow scarring and right now ruxolitinib is used to relieve symptoms. Pairing ruxolitinib with palbociclib may be a superior treatment.
“Current therapies only provide symptomatic relief without offering significant improvement of bone marrow fibrosis,” senior researcher Golam Mohi, PhD, of the University of Virginia School of Medicine’s Department of Biochemistry and Molecular Genetics, said in a statement. “So, there is a critical need to develop more effective therapy for myelofibrosis.”
Bone marrow scarring is the hallmark of myelofibrosis, and it disrupts the marrow’s production of blood cells, causes severe anemia, makes clotting difficult, and often causes an enlarged spleen.
The researchers found progenitor cells of myelofibrosis and other myeloproliferative neoplasms (MPNs) had significantly elevated CDK6 expression. They investigated the efficacy of palbociclib, a CDK4/6 inhibitor, alone or in combination with ruxolitinib in 2 different mouse models.
They found palbociclib alone or with ruxolitinib significantly inhibited hematopoietic cells expressing MPN driver mutants as well as markedly inhibited myelofibrosis in mouse models. Palbociclib’s effect of reducing spleen size and bone marrow scarring were “even more pronounced” than the effects seen with ruxolitinib.
In addition to being more effective, combining palbociclib and ruxolitinib will mean the dose of each can be lowered, which can reduce toxicities, the authors noted. They added that the results of their study support further investigation of the combination in patients to see if the findings translate.
“The findings from this study are very exciting, and they support the clinical investigation of palbociclib and ruxolitinib combination in patients with myelofibrosis,” Mohi said.
Reference
Dutta A, Nath D, Yang Y, Le BT, Mohi G. CDK6 is a therapeutic target in myelofibrosis. Cancer Res. Published online June 18, 2021. doi:10.1158/0008-5472.CAN-21-0590
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