Among patients with NPM1-mutant acute myeloid leukemia (AML), adjusted survival outcomes were similar following intensive induction chemotherapy (IC) and the combination of hypomethylating agents and Venclexta (venetoclax) (HMA/VEN), research has shown.
Results from an international, multicenter study evaluating these treatment options in 221 patients — 147 of whom were treated with IC and 74 of whom received treatment with HMA/VEN — older than 60 years were published in Blood Advances.
Glossary:
Intensive induction chemotherapy (IC): Induction chemotherapy, the first phase of treatment, lasts about a week, according to the American Cancer Society.
Hypomethylating agents (HMA): These are chemotherapy drugs that affect the way genes inside a cell are controlled, according to the American Cancer Society.
Venclexta (venetoclax, VEN): A daily oral drug that targets the BCL-2 protein, a protein which helps cancer cells live longer than they should, according to the American Cancer Society.
Composite complete remission (cCR): Complete response (the disappearance of cancer) plus complete response with incomplete blood count recovery
Overall survival (OS): The time a patient lives, regardless of disease status
Allogenic stem cell transplant: When a patient receives healthy stem cells from a donor.
Researchers noted that IC is the current standard of care for younger patients with AML, but stated that HMA/VEN treatment “can lead to durable remission among older patients” with NPM1-mutated disease.
Among patients with previously untreated NPM1-mutant AML, the rate of composite complete remission (cCR) was similar between the two treatment arms, at 85% among patients treated with IC and 74% among those who received HMA/VEN.
At first glance, overall survival (OS) was seen as favoring treatment with IC among unselected patients, with 24-month OS rates being 59% among patients treated with IC and 38% for patients who received HMA/VEN.
However, researchers explained in the study that OS was not significantly different for patients age 60 to 75 years. Patients who received IC demonstrated an OS rate of 60% compared with a rate of 44% in patients treated with HMA/VEN. These data were not significantly different among patients who received an allogenic stem cell transplant in addition to treatment, with OS rates of 70% and 66%, respectively.
“In this large, international, multicenter, retrospective analysis of patients aged ≥60 years with newly diagnosed NPM1-mutant AML, treatment with intensive induction chemotherapy was associated with similar cCR rates but longer OS when compared with HMA/VEN in unadjusted analyses,” researchers wrote in Blood Advances. “However, after initial adjustment for age of 60 to 75 years in the multivariable analysis, treatment type was no longer associated with OS. This indicates that other patient and disease characteristics have a greater influence on outcomes among patients with newly diagnosed, NPM1-mutant AML than the assignment of treatment modality.”
Multivariable analysis showed OS to not be statistically different between the two arms, with HMA/VEN demonstrating a 29% lower risk of death compared with treatment of IC.
On the other hand, further analysis showed that IC may be beneficial for patients with normal cytogenetics, with 24-month OS rates of 65% for IC and 40% for HMA/VEN, as well as for patients without FLT3 internal tandem duplication mutations, where 24-month OS rates were 68% for IC and 43% for HMA/VEN.
“Treatment with intensive induction chemotherapy and HMA/VEN resulted in similar OS in multivariable analyses after adjustment for important patient and disease characteristics,” researchers concluded. “Prospective randomized clinical trials are needed to ultimately determine the optimal frontline therapy for patients with NPM1-mutant AML.”
Reference
Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML” by Dr. Jan Philipp Bewersdorf, et al., Blood Advances.
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