A new study may help clear up questions about the superiority of venetoclax with hypomethylating agents in patients who are deemed to be at high risk of treatment-related mortality.
Patients with acute myeloid leukemia (AML) who are older in age had superior outcomes with venetoclax (Venclexta) and a hypomethylating agent compared with intensive chemotherapy (IC), according to new research.
The superiority was particularly notable in patients at high-risk of treatment-related mortality, the study found. The results were published in The American Journal of Hematology.
Patients who are older or otherwise unfit for IC are usually given venetoclax along with a hypomethylating agent (HMA), but corresponding author Marina Y. Konopleva, MD, PhD, of the University of Texas MD Anderson Cancer Center, and colleagues wrote that there is little data available to show how the venetoclax-HMA combination compares with IC in patients who are unfit for IC.
Konopleva and colleagues wrote that there have been lingering questions about the benefit of venetoclax and HMA regimens.
“These issues include questions about the proportion of truly ‘unfit’ patients in the clinical trials of venetoclax-based lower-intensity regimens and the appropriateness of the accelerated US Food and Drug Administration approval based on the earlier venetoclax trials,” they said.
Some question whether truly unfit patients might still benefit more from IC, and the investigators also noted that even the establishment of “fitness” can be murky and highly subjective.
In light of the uncertainty, Konopleva and colleagues sought to study how venetoclax and 10-day decitabine (Dacogen) would compare to IC in a cohort of both “fit” and “unfit” newly diagnosed patients with AML.
The authors constructed a retrospective analysis, in which they compared the results of 85 patients who were given daily venetoclax along with 20 mg/m2 of decitabine for 10 days (DEC10-VEN) for induction and decitabine for 5 days as consolidation with 85 patients who were given IC regimens containing cytarabine (Cytosar-U) ≥1 g/m2/d. The DEC10-VEN group was treated in 2018 and 2019; the IC group was treated between the years 2000 and 2018.
The DEC10-VEN group had a median age of 72 and 28% were considered to be at high risk of treatment-related mortality with IC, based on a validated TRM scoring system. The 2 groups were closely matched in terms of baseline characteristics, the authors said.
The authors found patients in the DEC10-VEN group had superior rates of complete response/complete response with incomplete hematologic recovery (CR/CRi), with 81% in the DEC10-VEN group achieving the status, compared to just 52% in the IC group. The DEC10-VEN group also had a lower rate of relapse (34% versus 56%), lower 30-day mortality (1% versus 24%), and longer overall survival (12.4 months versus 4.5 months).
“Even patients at high risk of TRM with intensive chemotherapy based on validated models did not experience increased early mortality with DEC10-VEN,” Konopleva and colleagues noted.
The investigators said the different eras in which the patients were treated ought to be considered when interpreting the results; however, the authors said many contemporary supportive care measures have been in place at the hospital for decades, and they said an event-free survival analysis showed a nearly identical benefit to the OS benefit in the study.
Overall, the investigators said, the data support the use of DEC10-VEN in older patients who are newly diagnosed with AML.
“Patients deemed at either high or low risk of early mortality with intensive chemotherapy appear to benefit from DEC10-VEN,” they concluded.
Maiti A, Qiao W, Sasaki K, et al. Venetoclax with decitabine versus intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment-related mortalityAm J Hematol. Published December 2, 2020. doi:10.1002/ajh.26061