Triplet therapy of azacitidine, venetoclax, and magrolimab was safe as first-line therapy in patients with acute myeloid leukaemia (AML) and displayed encouraging response rates and overall survival rates in a phase 1/2 study. The randomized phase 3 ENHANCE-3 trial has been initiated to assess whether this triplet combination can outperform the azacitidine and venetoclax doublet.
Dr. Naval Daver (Anderson Cancer Center) tested the combination of azacitidine, venetoclax, and magrolimab in a high-risk cohort of patients with newly diagnosed AML (N=43), and in two cohorts of patients with relapsed or refractory AML, either venetoclax-naïve (N=18) or venetoclax-experienced (N=18).1
In the frontline cohort, the complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 72%, and the CR rate was 49%. In addition, those with TP53-mutated disease and those with TP53-wildtype disease had comparable outcomes. After a median follow-up time of 14.5 months, the median overall survival (OS) was not reached in de novo patients (N=33) with TP53-wildtype (12-month OS 83%) or TP53-mutated AML (12-month OS 53%). In patients with secondary AML (N=10), the median OS times were 7.6 months and 9.6 months in those with TP53-mutated and TP53-wildtype disease, respectively.
Although 90% of the participants had at least one grade 3 or higher adverse event (AE), no study treatment discontinuations were reported due to treatment-related AEs. Finally, Dr. Daver noted that anaemia grade of at least 3 occurred in 23% of the participants and that this is an issue that should be monitored closely in following studies investigating the triplet combination of azacitidine, venetoclax, and magrolimab.
The phase 3 ENHANCE-3 trial will investigate the triplet combination versus azacitidine and venetoclax in patients with newly diagnosed, previously untreated AML. In the relapsed/refractory cohorts, the results were not promising, and Dr. Daver mentioned that it is unlikely that the triplet therapy will be further investigated in these patients.
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