“Standard treatment of older or less fit adults with acute myeloid leukemia (AML) is now venetoclax/azacitidine, which has been shown to improve overall survival vs azacitidine monotherapy. Since that backbone was established, there has been a tsunami of trials looking at drugs added to this backbone,’ said Mikkael Sekeres, MD, Chief, Division of Hematology and Professor of Medicine, University of Miami Health System and Sylvester Comprehensive Cancer Center.

Mikkael Sekeres, MD

“In a single-arm study, the anti-CD47 monoclonal antibody magrolimab had activity in myelodysplastic syndromes and AML. These provocative findings led to further study of magrolimab combined with azacitidine/venetoclax,” he continued.

“The study presented by Dr. Daver had a mixed bag of patients with AML—some newly diagnosed, some with relapsed or refractory disease, and some previously exposed to venetoclax. Objective response rates were high. There was a strong showing in the newly diagnosed cohort, with a response rate of 74%. Response rates were lower in the relapsed/refractory cohort, as you might expect,” he said.

“What I take from this study is there is a suggestion that combining magrolimab with venetoclax and azacitidine may lead to higher response rates in patients with AML. However, the caveat is that we have seen single-arm responses not pan out with further study. These data beg for results of a randomized trial with a more focused population of either newly diagnosed or relapsed/refractory patients with AML,” he noted.

Perspective on Pivekimab Sunirine

“The next abstract looked at pivekimab sunirine, an antibody-drug conjugate added to the standard backbone of venetoclax/azacitidine solely in patients with relapsed or refractory AML. Here’s where I’m going to quibble. I don’t like to use the definition of “morphologic leukemia-free state” [which was included in the objective response rate for this study]. This means the drug has wiped out the blasts, and it doesn’t matter what the peripheral counts are. I would focus on the composite rate of complete response—31%—which I consider respectable in relapsed/refractory AML. It remains to be seen whether this triplet actually provides an advantage over the standard backbone,” Dr. Sekeres concluded.

“The take-home message of these studies is that I am enthusiastic about triplets for patients with AML who are older or in the relapsed/refractory setting. All of the single-arm studies point out the need for randomized trials to demonstrate efficacy and safety,” he said. 

DISCLOSURE: Dr. Sekeres reported no conflicts of interest.