A recent phase II study published in Blood Advances indicates that low-dose subcutaneous decitabine (Dacogen) has therapeutic potential for treating myelofibrosis (MF). The multicenter trial demonstrated clinically meaningful overall response rates (ORR) and a favorable safety profile, suggesting that decitabine could be a valuable option for patients with this challenging disease.
The study, identified as NCT00095784, enrolled 21 patients with chronic-, accelerated-, and blast-phase MF. Participants received subcutaneous decitabine at 0.3 mg/kg/day on days 1-5 and 8-12 of a 42-day cycle until disease progression or unacceptable toxicity. The primary endpoints included response rates (complete and partial responses) and hematological improvement, along with overall safety. Secondary endpoints focused on epigenetic changes, hemoglobin F levels, and circulating CD34+ progenitor cell counts.
The results showed an ORR of 33% (95% CI, 15-57), primarily manifested as an improvement in cytopenias. The median duration of response was 7 months (range, 3-44). Researchers also observed associations between treatment with decitabine, high IPSS risk score, high baseline fetal hemoglobin level, and sustained decreases in circulating CD34+ cell counts.
Myelofibrosis is a rare myeloproliferative neoplasm (MPN) characterized by reduced blood cell production due to hematopoietic stem cell proliferation. The dysfunctional interaction between abnormal megakaryocytes and stromal cells leads to excessive fibrous tissue buildup and scarring in the bone marrow, resulting in severe anemia, weakness, and fatigue. Current treatment options are limited, often focusing on symptom palliation.
Decitabine, an FDA-approved chemotherapy agent, functions by incorporating itself into cancer cells’ DNA and inhibiting DNA methylation, reactivating silenced tumor suppressor genes. It has also been shown to induce differentiation of bone marrow cells, potentially normalizing bone marrow function in some patients.
While all patients experienced at least one grade 3 or 4 cytopenia, the treatment exhibited a favorable safety profile with a low frequency of non-hematologic toxicities. The most common non-hematologic toxicities included fatigue, anorexia, and hypocalcemia.
"The results suggest the need for further research into decitabine as a potential therapeutic option for patients with MF," the researchers noted. Decitabine may pave the way for therapies that go beyond symptom palliation and effectively treat MF, addressing a significant unmet medical need.
