Novel Drug Regimen Shows Significant Benefits in Acute Myeloid Leukemia


Newly diagnosed patients with FLT3-mutated acute myeloid leukemia showed improvements after receiving crenolanib plus chemotherapy in a recent study.

blood cells and research images

A novel cancer regimen is showing promise in treating certain patients with acute myeloid leukemia.

A novel treatment combination demonstrated promise for patients with acute myeloid leukemia (AML) who have FLT3 mutations, according to recent research from Roswell Park Comprehensive Cancer Center.

In particular, crenolanib plus intensive chemotherapy led to improved overall response rates, prolonged event-free survival (time after treatment when the cancer does not return) and overall survival, according to a news release from Roswell Park.

Overall response rate (ORR) is the percentage of patients who have a partial or complete response to treatment, as the National Cancer Institute defines. The institution also defines overall survival (OS) as the time from either diagnosis or the start of treatment when a patient with cancer is still alive.

Crenolanib is an FLT3 inhibitor that binds to the gene FLT3 to prevent the growth of more cancer cells, according to the National Cancer Institute. The study determined that the drug is also used in patients whose cancer may resist other tyrosine kinase inhibitors (TKIs).

“In this trial, the combination of crenolanib after intensive chemotherapy in fit adults with newly diagnosed FLT3-[mutant] AML appears to be safe and tolerable with promising efficacy,” wrote the researchers of the study. “Unlike other TKIs which are limited to 14 days per cycle because of toxicities, crenolanib was continuously administered for weeks to months without significant dose reductions or drug-drug interactions because of azoles, cardiotoxicity, or delayed count recovery.”

The study included 44 patients who were between the ages of 19 and 75 years old and had recently received diagnoses of FLT3-mutated AML. Of 44 total patients, 36 were reported to have FLT3-ITD mutations and 11 had FLT3-TKD mutations.

The researchers found that the ORR was 86% and 77% of patients had a complete response to the treatment with no evidence of disease. Patients who were younger than age 60 had higher response rates of 90%, although patients aged 60 or older had response rates of 80%, the study established.

The median event-free survival was 44.7 months at a 45-month follow-up, researchers found. They also determined that the OS was not reached because more than half of the patients were still alive. Of note, 55% of patients were still alive three years after treatment, in which approximately 67% of patients were aged 60 or younger.

“Although not confirmed by plasma inhibitory assays, prolonged and potent FLT3 suppression may account for long-term benefit,” the researchers wrote.

Researchers reported that all patients had at least one side effect after receiving the crenolanib-intensive chemotherapy regimen. The most common treatment-emergent side effects were diarrhea, nausea, vomiting, febrile neutropenia (fever caused by low levels of white blood cells) and peripheral edema (swelling in legs from fluid retention in leg tissues), according to the study.

Serious side effects occurred in 30 of the 44 patients, with 22 patients experiencing febrile neutropenia, the researchers noted. Three deaths occurred: two because of sepsis (the body’s improper response to an infection) and one because of respiratory failure. Eight patients had discontinued treatment after induction, although six patients underwent reinduction, the study stated.

“Thirty-seven patients continued full dose crenolanib during induction, with seven (four older than 60 years) requiring dose reductions because of liver dysfunction, edema, vomiting, rash, and melena (dark stools),” the researchers wrote.

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