Jakafi and Dacogen May Improve Overall Survival in Patients with MPN


Patients with myeloproliferative neoplasm (MPN) may benefit from this combination treatment if they are in the accelerated or blast phase of the disease.

Results from a phase 2 study demonstrated that treatment with Jakafi (ruxolitinib) and Dacogen (decitabine) was well tolerated and contributed to favorable overall survival (OS) in patients with myeloproliferative neoplasm (MPN) in the accelerated or blast phase.

MPN is a blood cancer that develops when a stem cell mutation in the bone marrow leads to an overproduction of white cells, red cells and/or platelets. The accelerated phase of MPN refers to when 10% to 19% of blasts, or immature blood cells, are in the blood circulating through the body or in the bone marrow, whereas the blast phase refers to 20% or greater blasts in the circulating blood or bone marrow, according to the study published in Blood Advances.

“This study was important, as patients with an antecedent (pre-existing) myeloproliferative neoplasm that evolves into an acute myeloid leukemia have a dismal prognosis of several months, and induction chemotherapy alone does not improve outcome unless followed by consolidation hematopoietic stem cell transplantation,” Dr. John O. Mascarenhas, director of the adult leukemia program and leader of the myeloproliferative neoplasm clinical research program at Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, said in an interview with CURE®.

The study authors previously assessed this therapy in a multicenter, phase 1 trial.

“We had previously shown that the epigenetic modifying agent decitabine can be administered (on) an outpatient (basis) and improve outcome with a median survival of nine to 10 months,” Mascarenhas said. “This prospective, phase 2, multicenter, investigated-initiated trial built on the phase 1 trial of combination decitabine and ruxolitinib based on supportive preclinical data from the laboratory of our collaborator, (Dr.) Ross Levine.”

In this current trial, 25 patients (median age, 71 years; 56% women) with MPN either in the accelerated phase (10 patients; median age, 70.1 years; 70% women) or blast phase (15 patients; median age, 71.6 years; 46.7% women) were treated with Jakafi and Dacogen. A 25 mg dose of Jakafi was administered orally twice per day for 28 days in addition to a 20 mg/m2 dose of Dacogen intravenously during days 8 through 12. After that first cycle, the dose of Jakafi was reduced to 10 mg.

The prespecified primary endpoint, or goal, was best response by six months, and the predetermined secondary endpoint focused on the safety and tolerability of Jakafi and Dacogen. Study authors defined OS as the time from the first dose of Jakafi to death from any cause.

During follow-up, 19 patients died from causes including respiratory failure, disease progression, sepsis and pneumonia. Patients in this study had a median OS of 9.5 months. Overall response rate, which included complete remission, incomplete platelet recovery and partial remission, occurred in 44% of patients. Response to this treatment was not linked with improved survival.

“This combination is well tolerated and can provide spleen symptom benefit and survival advantage compared to cytotoxic chemotherapy,” Mascarenhas said. “This study supports the use of this approach to maintain ambulatory care of these very advanced patients with a limited lifespan. This is one therapeutic approach that is now included in the (National Comprehensive Cancer Network) guidelines.”

Mascarenhas added that more research is needed in this area. “Ultimately, we need to identify active agents that can fully eliminate the malignant hematopoietic stem cell and attain molecular remissions that afford patients long-term survival,” he said. “This is an ongoing area of active translational research of our group.”

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