Researchers observed encouraging response rates in older or high-risk patients with newly diagnosed acute myeloid leukemia (AML) when treated with the triplet combination therapy of azacitidine, venetoclax, and magrolimab in a phase I/II trial, according to new findings presented by Daver et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 61). The patients involved in the study demonstrated an 80% overall response rate, and the median overall survival was not yet reached at a median follow-up of 9.2 months.
“We are encouraged by the promising evidence of this triplet therapy as a treatment option for older or unfit patients with AML,” said lead study author Naval Daver, MD, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “We will continue to expand the trial to include more patients, and we have initiated an international phase III randomized study evaluating the triplet therapy vs the doublet azacitidine/venetoclax. If the study is positive, it could establish a new front-line standard of care for these patients.”
About 50% to 55% of patients with AML are considered older or unfit for intensive chemotherapy. Front-line treatment with azacitidine and venetoclax may achieve response rates of 65% to 70% in newly diagnosed patients, but most of them will relapse—and those with TP53 gene mutations continue to have poor outcomes, with a median overall survival of less than 6 months. Magrolimab is an anti-CD47 antibody that works to block the “don’t eat me signal” on leukemia cells. In a previous trial, magrolimab demonstrated efficacy with azacitidine in newly diagnosed AML, with an especially encouraging signal of response and survival in front-line TP53-mutated AML.
In the new trial, researchers enrolled 74 patients across two cohorts. The first cohort included 45 front-line patients aged over 74 years with documented comorbidities that made them ineligible for intensive therapy—or with adverse risk factors and/or a TP53 gene mutation, regardless of age. Among the patients in the first cohort, 27 of them had a TP53 gene mutation and 14 did not have the mutation. The second cohort involved 29 patients with relapsed or refractory disease.
All patients who received at least one dose of any of the three study drugs were included for response and adverse events. Eighteen patients experienced greater than grade 3 anemia, and the most common nonhematologic side effects were febrile neutropenia, pneumonia, hyperbilirubinemia, transaminitis, creatine elevation, and hypokalemia.
In the newly diagnosed cohort, the overall response rate in patients with and without TP53 gene mutations was 74% and 93%, respectively. The median overall survival was not yet reached for either group of patients. Responses in patients with relapsed/refractory disease with prior venetoclax treatment were modest, and the cohort was closed for futility. Patients with relapsed/refractory disease without venetoclax exposure are still being enrolled.
Disclosure: The research in this study was funded by Gilead. For full disclosures of the study authors, visit ash.confex.com.
