Preventing Myelofibrosis from Progressing to Acute Myeloid Leukemia

Myelofibrosis, a type of myeloproliferative neoplasm (MPN), typically moves through two stages — chronic and accelerated – before reaching the blastic phase and turning into acute myeloid leukemia (AML). Diagnosing and treating the disease before it turns into AML is a key area of study, said Srdan Verstovsek, M.D., Ph.D., medical oncologist and professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

“A lot of effort is spent on understanding the transformation from chronic phase to blastic phase to AML because AML is very deadly,” Verstovsek said in an interview with OncLive, a sister publication of CURE. “Overall survival is about six to eight months. We put a lot of effort in treating and understanding how to benefit patients with AML that happens after myelofibrosis.”

The disease phase can be classified by the amount of atypical blood-forming cells called myeloblasts (commonly referred to as just “blasts”) in a patient’s blood. Patients with 0 to 10 percent blasts are in the chronic phase; 10 to 20 percent are in the accelerated phase; and 20 percent is the blastic phase, AML.

But Verstovsek mentioned that better measures are needed to determine the different phases and suggested that researchers start looking at certain molecular findings, or karyotype or chromosomal changes. Then, it would be a matter of getting the right intervention.

“If we can focus on this group of patients who are in transition, from more chronic and stable condition to blastic phase, then we can implement therapies earlier on and save their life or direct them to a transplant — the only possibility to cure them – sooner,” he said, noting that it is important to recognize this transitional phase and implement earlier therapy with hypomethylation agents, too, including chemotherapy agents such as azacitdine and decitabine.

Even so, these agents are not a cure-all, as their main function is just to control symptoms.

“Hypomethylating agents are provided to patients with accelerated- and blastic-phase disease because they have a potential to lower blasts. They cannot control disease,” Verstovsek said. “There are even reports of some complete responses and some partial responses, but the goal is really to put back patients in the chronic phase and then get them to transplant to save their life. “

If that is not possible, Verstovsek said, then patients can continue on the hypomethylation therapy, perhaps even introducing chemotherapy or the JAK inhibitor Jakafi (ruxolitinib) to control spleen and liver symptoms and improve quality of life.

But again, Jakafi is not the magic bullet needed in treating this disease.

“In fact, the use of ruxolitinib, the only approved JAK inhibitor, is endorsed very much by NCCN (National Comprehensive Cancer Network) guidelines for patients with accelerated- or blastic-phase, regardless of their blood cell counts, to use in an appropriate dose in the individual setting that will be there to control the symptoms, not to do anything about the blasts or progressive nature of the disease,” he said.

Ultimately, more work is needed in preventing myelofibrosis from turning in to AML, thus greatly extending patients’ lives.

“We call myelofibrosis a chronic disease, but it doesn’t stay chronic forever,” Verstovsek said.